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This study presents evidence of a probable case of holoprosencephaly with cyclopia, which has been rarely reported in the paleopathological literature. The skeletal remains of a male fetus between 36 and 40 gestational weeks from the Collezione Antropologica LABANOF (CAL) Milano Cemetery Skeletal Collection were studied. The bones were macroscopically examined, and pathological anomalies were recorded and evaluated alongside paleopathological and clinical literature. Developmental anomalies were observed. In particular, a single orbit and