According to Padre José Santiago Crespo del Pozo's Blasones y linajes de Galicia, the Sande are an ancient and illustrious Galician lineage traditionally claiming descent through the male line from the royal family of Count Hermenegildo Gutiérrez (c. 850 — after 912), Mayordomo Mayor of King Alfonso III of Asturias. Hermenegildo was a magnate of immense power: repopulator and Count of Coimbra, his daughter Elvira became Queen Consort of León as wife of King Ordoño II. Their son Sancho Ordóñez became the first King of Galicia (926–929); like most medieval monarchs his court was itinerant, but the Miño valley remained closely tied to his royal household — he was buried at the monastery of Castrelo de Miño, and his widow Goto Muñiz stayed on as its abbess. Over a century later, Garcia II — a direct descendant of Ordoño II and Elvira through the Leonese royal line — chose nearby Ribadavia as the capital of his Kingdom of Galicia (1065–1071).

From this exalted line descended Don Juan de Sande, who established himself as lord of the valley and castle of Sande in the parish of San Salvador de Sande, municipality of Cartelle, in the Terra de Celanova. The Sande family name is toponymic, derived from the Latin sabulum (coarse sand), marking the sandy alluvial soils where the Arnoia and Miño rivers converge below the fortress. The earliest documented reference to the Sande surname in Galicia dates to 1274.

The defining event in the early history of the Casa de Sande was an act of violence whose roots lay in the entangled history of a noble family and a monastic institution. The lords of Sande and the founder of the Monastery of San Salvador de Celanova shared a common ancestor: Count Hermenegildo Gutiérrez (c. 850–912), the mayordomo mayor of King Alfonso III and conqueror of Coimbra. His son, Count Gutierre Menéndez, was the most powerful magnate in 10th-century Galicia, and his grandson San Rosendo — bishop, viceroy, and celibate Benedictine monk — founded the Monastery of Celanova in 936 on lands donated by his own brother, Count Froila Gutiérrez. From this same stock, according to Padre Crespo's Linajes y Blasones de Galicia, descended the lords of Sande, who held the Torre de Sande as their ancestral seat overlooking the valleys of the Arnoia and Miño rivers. But San Rosendo left no heirs: within a generation, Celanova became an autonomous Benedictine institution governed by elected abbots with no blood ties to the family that had endowed it. Over the centuries, these abbots accumulated vast territorial holdings, priories across Ourense and beyond, and titles including Count of Bande, Marquis of the Torre de Sande, and Chaplain of the Royal House. Prolonged territorial clashes erupted between the monastery and the secular Sande lords, culminating in an act of extraordinary gravity: Nuño de Sande, Señor del Castillo y Valle de Sande, killed the abbot of Celanova during one of these confrontations. In medieval Galicia, where monasteries held immense spiritual and temporal authority, the murder of such a churchman demanded the harshest royal response.

The killing precipitated — or provided the justification for — a definitive royal confiscation. King Alfonso VII of León and Castile, together with Queen Berenguela of Barcelona, issued a charter on 5 May 1141 in Zamora, donating the Castle of Sande — with all its hereditary lands, jurisdictional rights, and revenues — to the Monastery of San Salvador de Celanova. The confiscation was definitive: the Sande family lost their ancestral fortress to the very institution their ancestor's relative had founded two centuries earlier. The abbots of Celanova thereafter held the title of Marquises of the Tower of Sande — the family name now adorning a monastic dignity. This donation was later confirmed by Alfonso IX of León, and the original Latin parchment (378 × 430 mm, in Caroline script showing Gothic influences) survives in the Archivo Histórico Nacional.

Reduced in status after the 1141 confiscation, and with their ancestral fortress later destroyed by the irmandiños, the Sande family gradually dispersed across the Iberian Peninsula. The first Sande knight to leave Galicia for Extremadura donated his remaining Galician lands to the Convent of Celanova before departing south, establishing the family in Cáceres, where they became part of the urban lower nobility.

Meanwhile, Lopo Afonso de Sande fled to Portugal at the beginning of the reign of João I (c. 1385), reportedly after defenestrating an abbot of Celanova — an echo, perhaps, of the original crime. His brother Pedro Lopes de Sande remained in Castile. From these branches arose extraordinary figures: Álvaro de Sande (c. 1489-1573), hero of the Spanish Tercios who captured the Elector of Saxony at Mühlberg; Francisco de Sande y Picón (c. 1540-1602), Governor of the Philippines who founded Nueva Cáceres; Rui de Sande, ambassador of João II whose diplomacy led to the Treaty of Tordesillas (1494); and Francisco de Melo e Torres, 1st Marquis of Sande, who negotiated the marriage of Catherine of Braganza to Charles II of England.