Background: Extremities are peculiar sites of origin for rhabdomyosarcomas (RMS) and are usually associated with an unfavorable outcome. Methods: The authors reviewed the clinical data on 60 patients <21 years old with limb RMS treated at the Pediatric Oncology Unit of the Istituto Nazionale Tumori of Milan, in Italy, over a 30-year period. Twelve patients had tumors arising in the hand and foot. Results: Complete tumor resection was achieved in 21 patients (but in only 1 case of hand/foot RMS); all patients received chemotherapy and 43 also had radiotherapy. The alveolar subtype was identified in 62% of cases. Half of the hand/foot cases had metastatic disease at onset. Overall survival at 5 years was 33% among the hand/foot cases and 56% for the others. Most of the relapsing cases had distant metastases. Conclusions: A particularly poor survival was observed for RMS of the hand/foot due its marked tendency to spread. Surgical resection is particularly difficult in such cases and a multimodality treatment approach seems crucial to improving their outcome.