Surgical prophylaxis of malignant melanoma. A review of a 14-year experience with prophylactic pigmented skin lesion removal is presented. Data obtained during a 4-year interval of this 14-year experience is analyzed specifically. During this 4-year interval, 250 patients with melanoma were seen. Of these patients, 75 with a history of stage I (localized) melanoma and three patients with stage II (history of controlled regionally metastatic melanoma) underwent removal of multiple skin lesions on a prophylactic basis. Of the removed lesions, 28% showed hyperplasia, atypia, dysplasia, or melanoma. Nine unsuspected in situ, or level I melanomas, and three unsuspected invasive melanomas were removed from these 75 melanoma patients while excising lesions prophylactically during the 4-year interval. It is estimated that four to six additional melanomas were prevented by excision of precursor lesions. During the same 4-year interval, an additional 112 of approximately 1000 patients without a previous history of melanoma underwent prophylactic lesion removals. In 31% of the 112 patients, there was a history of melanoma in a first-degree relative. In 22% of the removed lesions there was hyperplasia, atypia, or dysplasia. Three cases of melanoma in situ were detected and it is estimated that an additional three to five cases of melanoma were prevented. Atypical findings occurred in 71, or 63%, of the patients biopsied, which represented 7% of the approximately 1000 patients screened. During the 4-year interval, an average of 17.7 lesions were removed from each of the 190 melanoma and nonmelanoma patients undergoing prophylactic skin lesion excision. This was accomplished in one to four sessions per patient. This average reflects only those patients who underwent one excision or more and does not include those patients treated without operation. When including the nonoperated patients screened during this interval, the average number of lesions removed was 2.7 per patient. Death from new melanomas was prevented during the 14-year period of this study as evidenced by the fact that no patient died or developed metastatic disease from a cutaneous melanoma that was not apparent or known about at the time of first examination. 