Beckwith–Wiedemann syndrome BWS is an overgrowth syndrome characterized by macroglossia, macrosomia, and abdominal wall defects. It is a multigenic disorder caused in most patients by alterations in growth regulatory genes. A small number of individuals with BWS 5–10 have mutations in CDKN1C, a cyclindependent kinase inhibitor of G1 cyclin complexes that functions as a negative regulator of cellular growth and proliferation. Here, we report on eight patients with BWS and CDKN1Cmutations and review previous reported cases. We analyzed 72 patients 50 BWS, 17 with isolated hemihyperplasia IH, three with omphalocele, and two with macroglossia for CDKN1Cdefects with the aim to search for new mutations and to define genotype–phenotype correlations. Our findings suggest that BWS patients with CDKN1Cmutations have a different pattern of clinical malformations than those with other molecular defects. Polydactyly, genital abnormalities, extra nipple, and cleft palate are more frequently observed in BWS with mutations in CDKN1C. The clinical observation of these malformations may help to decide which genetic characterization should be undertaken i.e., CDKN1Cscreening, thus optimizing the laboratory evaluation for BWS. © 2010 WileyLiss, Inc.