A retrospective study of imaging-directed percutaneous fine-needle aspiration cytology of focal renal lesions was performed. The objectives were to determine the efficacy and safety of renal aspiration biopsy in establishing the diagnosis of renal cell carcinoma and avoiding nephrectomy in patients with a renal mass and disseminated metastases or with a renal mass and relative contraindications to nephrectomy. Between September 1987 and September 1991, 55 consecutive patients had 57 imaging-directed renal aspiration biopsies at our institution. We examined the medical records, pathology reports, imaging studies, and follow-up information of the 23 patients who had the procedure because of disseminated metastases (10 patients) or relative contraindications to nephrectomy (13 patients). Preliminary diagnoses were based on the cytopathology, and final diagnoses were based on the surgical pathology (six patients) or clinical course over more than 6 months (17 patients). Cytopathologic findings were true-positive in 12 patients, true-negative in eight, false-negative in three, and false-positive in none. The sensitivity was 80%, the specificity was 100%, and the accuracy was 87%. Of the 10 patients with a renal mass and disseminated metastases, aspiration cytology failed to show malignancy in only one. None of these patients had surgery, and all died within 1 year. Of the 13 patients with relative contraindications to surgery, seven were treated without surgery. The cytologic diagnosis was renal cell carcinoma in two of the seven, and these two patients have since died. Cytopathology was negative for renal cell carcinoma in five of the seven, and subsequent imaging studies in these patients have shown no renal mass enlargement or metastases 2-3 years after biopsy (three patients) or the patients have died of severe heart disease (two patients). Nephrectomy was performed in the remaining six patients, and no evidence of disease had been found 2-4 years after removal of two oncocytomas and four renal cell carcinomas. There were no significant complications. Percutaneous renal aspiration biopsy cytology is accurate, safe, and useful in establishing the diagnosis of renal cell carcinoma in patients with disseminated metastases or relative contraindications to surgery.