Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, accounts for 3% of childhood malignancies. Multiple Endocrine Neoplasia (MEN) type 2A is an autosomal dominant syndrome associated with near universal development of medullary thyroid carcinoma. We describe a previously unreported association of MEN-2A with metastatic alveolar RMS and review the literature on associated hereditary cancer predisposition syndromes and current therapeutic options. The high penetrance of malignancy in patients with MEN warrants a heightened suspicion for the development of nonendocrine malignancies. The diagnosis of RMS should prompt consideration of screening for familial genetic syndromes in certain patients.