Between July 1992 and June 1996, 3934 new cases of acute leukaemia were registered in the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Archive of Adult Acute Leukaemia. Two hundred cases (5·1%) presented with a history of primary malignancy (PM), 179 of which were acute myeloid leukaemia (AML). The median age of these cases was significantly higher than that of other primitive AML (63 years vs. 57 years;P < 0·001). The number of men was significantly lower than the number of women [74/1544 (4·8%) vs. 105/1420 (7·4%); odds ratio (OR) 0·63, 95% confidence interval (CI) 0·46–0·87;P < 0·002], as was the number of patients aged < 65 years [104/1963 (5·3%) vs. 75/1001 (7·5%); OR 0·69, 95% CI 0·50–0·95;P < 0·01]. An increased incidence of cancer was observed among first-degree relatives of patients with AML occurring after a PM (secondary AML; sAML) [66/179 (36·9%) sAML vs. 757/2785 (27·2%) de novo AML, age adjusted; OR 2·62, 95% CI 1·07–6·42;P < 0·005]. Prevalent types of PM were breast cancer, lymphoma and Hodgkin's disease. sAML occurred after a median latency of 52 months (range 2–379). Of the 122 patients who received chemotherapy for sAML, 67 patients (55%) achieved a complete remission (CR), three a partial remission, 15 (12%) died in induction and 37 (30%) were unresponsive. The median duration of CR was 30 weeks (range 4–250). The median overall survival was 7 months (range 1–196). Comparing acute promyelocytic leukaemia with all other French–American–British (FAB) groups, a significant increase in CR achievement was observed [14/18 (77·7%) vs. 53/101 (52·4%), P < 0·046] as well as in median CR duration (55 vs. 24 months, P < 0·02). The analysis of our data suggests that not only previous chemotherapy but also genetic predisposition could play a role in the pathogenesis of sAML.