The authors describe the incidence of new primary cancers among 4,639 cases of squamous cell skin cancer (SCC) diagnosed between 1974 and 1994 in the cancer registries of the Swiss cantons of Vaud and Neuchâtel (total person-years at risk = 23,152). Overall, 729 metachronous cancers were observed versus 527.6 expected, corresponding to a standardized incidence ratio (SIR) of 1.4 (95% confidence interval (CI) 1.3-1.5). After exclusion of skin cancers, however, 384 second primary neoplasms were observed versus 397.2 expected (SIR = 1.0). Excesses were observed for cancers of the lip (SIR = 3.1) and lung (SIR = 1.3), for basal cell (SIR = 4.3) and melanomatous skin cancers (SIR = 3.3), and non-Hodgkin's lymphomas (SIR = 1.7). Rates were elevated for cancers of the salivary glands (SIR = 4.3) and for Hodgkin's disease (SIR = 2.7), and, below age 65 years, for cancers of the lung (SIR = 1.6), breast (SIR = 1.5), and prostate (SIR = 1.8), for Hodgkin's disease (SIR = 15.8), as well as for all neoplasms except skin (SIR = 1.2; 95% CI 1.0-1.5). The cumulative risk of basal cell skin cancer reached 17% after 15 years. The authors believe that the excesses for basal cell carcinomas and melanomas of the skin following SCC, and possibly of lymphomas, were likely attributable to common phenotypic characteristics and exposure to UV radiation. The elevated rates of lung cancer are suggestive for a role of tobacco as a cause of squamous cell skin cancer.