OBJECTIVE: To describe the mucocutaneous and soft tissue infections caused by Xanthomonas maltophilia in patients with cancer. DESIGN: A retrospective 15-month clinical study. SETTING: Academic, referral-based cancer center. PATIENTS: Of 237 patients with X. maltophilia isolated from all sites during the 15-month study period, 114 patients were judged to have true X. maltophilia infections. Only patients with mucocutaneous and soft tissue infections were included in the study. RESULTS: 17 (15%) of the 114 patients with X. maltophilia infection had mucocutaneous and soft tissue infections: Six patients had metastatic cellulitis, 5 had primary cellulitis usually associated with catheter use, and 6 had infected mucocutaneous ulcers. The metastatic cellulitis consisted of previously undescribed multiple, hard, tender nodules with surrounding and distant cellulitis (5 patients) or ecthyma gangrenosum (1 patient). Four of these patients died of the infection. Metastatic cellulitis and mucocutaneous infections occurred in hospitalized, neutropenic patients who received broad-spectrum antibiotics (beta-lactams, quinolones), often with in vitro activity against the infecting organisms. Response usually correlated with recovery from myelosuppression and administration of trimethoprim-sulfamethoxazole with or without ticarcillin-clavulanate. Catheter removal contributed to response in the treatment of primary cellulitis. CONCLUSIONS: Mucocutaneous and soft tissue infections caused by X. maltophilia are not uncommon, and X. maltophilia can cause metastatic nodular skin lesions that mimic disseminated fungal infections. It also causes serious morbidity and high mortality in patients with metastatic skin nodules and can cause superinfections in patients receiving broad-spectrum beta-lactam or quinolone antibiotics to which the organisms are susceptible when the infections develop. Catheter removal contributes to a favorable outcome in patients with catheter-associated cellulitis without bacteremia. Xanthomonas maltophilia infection should be added to the differential diagnosis of mucocutaneous or soft tissue infection in patients with cancer. Trimethoprim-sulfamethoxazole with or without ticarcillin-clavulanate is the current treatment of choice for culture-proven infections, but early empiric therapy may improve outcome.