Buschke-Ollendorf syndrome (BOS) is an autosomal dominant genodermatosis associated with heterozygous loss-of-function germline mutations in the LEMD3 gene. It is characterized by small, acquired, asymptomatic foci of osteosclerosis (osteopoikilosis [OPK]) along with connective tissue nevi. In this case series, Yadegari et al describe a father and son with nevus elasticus along with radiographic evidence of OPK. These clinical findings were diagnostic of BOS, but LEMD3 gene analysis revealed no exonic mutations, which suggests genetic heterogeneity for BOS. Mechanisms for this heterogeneity include mutations in intronic sequences, promoter region defects, complete exonic deletion, or an entirely different gene defect.