We have studied the frequency of second primary malignancies (SPM) among the 2,328 children registered in 1967-1969 at the Childhood Cancer Registry of Piedmont, the largest population-based childhood cancer registry in Southern Europe. Since the population of Piedmont is not served by a conventional cancer registry covering all ages, SPMs were identified through a number of ad hoc surveys within a variety of sources. Eighteen SPM (all histologically diagnosed) were observed after a thorough survey conducted in the ontological departments in Piedmont and after a postal questionnaire addressed to general practitioners. Death certificates were also examined. The crude incidence rate was 116.5 per 100,000 person-years. Risk was higher among children whose first malignancy was diagnosed more recently (SIR = 9.8 for diagnoses in 1983-1989 vs. 4.5 for diagnoses in 1967-1974). The same tendency was confirmed in analyses restricted to children in whom leukemia was diagnosed as the first cancer. Clinical data regarding the treatment of the first malignancy were available for 16 children out of 18: 15 had received chemotherapy and 12 radiotherapy (9 SPM originated in the irradiation field). The interest of measuring the risk of SPM on a population basis (and not only in clinical series) and the advantage of close cooperation between epidemiologists and clinical oncologists are underlined.