Hodgkin lymphoma (HL) is a highly curable disease owing to remarkable advances in treatment. However, potential long-term complications of the disease, such as the development of second primary tumors (SPTs), are a major concern for survivors of HL. In the present study, we used cytogenetic biomarkers to identify HL patients at risk of SPTs. Our study cohort consisted of 251 HL patients; the mean follow-up time was 17.3 years. The mean number of chromatid breaks in patients who developed SPTs (3.52 ± 0.43) was significantly higher than that in patients who did not develop SPTs (2.43 ± 0.13; P<0.01). Chromosome aberration level and patient age at diagnosis were predictors of SPT development. G-banding revealed that patients who developed SPTs had significantly more structural abnormalities involving chromosomes 2, 4, 11, 14, and X than did patients who did not develop SPTs. Structural changes in chromosome 5 occurred exclusively in HL patients with no SPTs, whereas chromosome 9 and 16 involvement were present exclusively   in HL patients with SPTs. Although patients with and patients without SPTs had t(8;14) and t(11;14) chromosomal translocations, the frequency of chromosomal translocations was significantly higher in patients with SPTs than in patients without SPTs. This novel finding suggests that structural chromosome changes in HL patients who develop SPTs are not randomly distributed. Therefore, chromosome aberration analysis may have a role in identifying HL patients at high risk of SPTs and thus, the potential to improve early detection and prevention strategies.