BACKGROUND: The eruptive appearance of numerous seborrheic keratoses, the sign of Leser-Trélat, has been regarded as a reliable cutaneous marker of internal malignancy. OBJECTIVE: We have evaluated the possible association of malignant disease and the sign in 1752 consecutive cases of seborrheic keratoses. METHODS: First, the Swedish Cancer Registry was searched for records of malignancies in the study population (1958 to 1984), and the expected number of malignancies was calculated. Second, records of persons with malignancy within 1 year before or after the diagnosis of seborrheic keratosis were checked for the sign of Leser-Trélat. Third, a case control study was performed to evaluate the possibility of eruptive seborrheic keratoses among the noncancer patients in the study population. RESULTS: The results showed a slight increased risk of cancer in the study population (relative risk = 1.2; 95% confidence interval = 1.0 to 1.3), mainly because of an increased risk of cutaneous squamous cell carcinoma. In 62 patients with seborrheic keratoses, a malignancy (excluding skin) was diagnosed within 1 year before or after the diagnosis of seborrheic keratosis. Of these 62 patients, 6 were regarded as possibly having presented with the sign of Leser-Trélat. For every one of the 62 cases with seborrheic keratosis and malignancy within one year, an age- and sex-matched control patient without cancer was selected from the study population and the records were checked for sudden and eruptive seborrheic keratoses. Among the control patients, five were regarded as possibly having presented with the sign of Leser-Trélat. CONCLUSION: This study gives no evidence to support the opinion that eruptive seborrheic keratoses are related to internal cancer risk.