In this report we describe a 6-year-old boy with Sotos syndrome and a de novo apparently balanced 3/6 translocation (karyotype: 46,XY,t(3;6)(p21;p21)). Pre- and postnatal overgrowth are observed in an increasing number of conditions of variable etiology. In the Sotos syndrome autosomal dominant inheritance with variable expression has been documented. Here we discuss the importance of the cytogenetic findings and postulate a relationship between the invisible loss of chromosomal material at 3p21 and/or 6p21 and the expression of the autosomal dominant gene.