A study of 24 patients with proved malignant tumors originating in smallpox vaccination scars is reported. Three different tumor types were found—malignant melanomas, basal cell carcinomas, and squamous cell carcinomas. There was no exposure to known chemical carcinogens. In most cases a primary vaccination site was involved. The period of time between the vaccination and appearance of the malignant tumor was highly variable. Twenty-three of the patients were from various regions of the United States and one from the Republic of South Africa. Two patients presented tumors in vaccination sites bilaterally. The possible role of vaccinia virus in the present cases is unknown and difficult to conceive. However, it is suggested that additional clinical, epidemiological, and laboratory studies should be made to determine the role, if any, of vaccinia virus in the development of malignant tumors in man.