We report the unusual case of a 72-year-old man who developed acute and extensive necrosis of the nasal skin and soft-tissue envelope while undergoing chemotherapy for Waldenström's macroglobulinemia, a lymphoproliferative disorder. The patient's treatment involved infusions of rituximab, a chimeric monoclonal antibody that is directed against B cell surface membrane protein CD20. The patient refused surgery to restore the nose, and he was treated conservatively with wet-to-dry dressings and antibiotic ointment. Approximately 5 weeks after admission, the eschar had exfoliated, revealing that the underlying skin was pink and healthy; no significant areas of necrosis remained. Within weeks, the nose had healed completely without scarring. A good aesthetic result was achieved exclusively through healing by secondary intention. We wish to alert the medical community that (1) conservative management of even extensive nasal skin loss should be considered when clinically acceptable, and (2) there may be an association between anti-CD20 antibody therapy for Waldenström's macroglobulinemia and skin necrosis.