The aim of this study was to evaluate the association between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), thyroid cancer (TC), chronic lymphatic leukemia (CLL), acute lymphatic leukemia (ALL), and Hodgkin's lymphoma (HL). A Swedish cohort of 27,150 HCV-infected persons notified during 1990-2000 was included in the study. The database was linked to other national registers to calculate the observation time, expressed as person-years, and to identify all incident malignancies in the cohort. The patients were stratified according to assumed time of previous HCV infection. The relative risk of malignancy was expressed as a standardized incidence ratio (SIR)-the observed number compared to the expected number. During 1990-2000 there were 50 NHL, 15 MM, 14 ALL, 8 TC, 6 CLL, and 4 HL diagnoses in the cohort. Altogether, 20 NHL, 7 MM, 5 TC, 4 CLL, 1 ALL, and 1 HL patient fulfilled the criteria to be included in the statistical analysis. The observation time was 122,272 person-years. The risk of NHL and MM was significantly increased in the stratum with more than 15 years of infection (SIR 1.89 [95% CI, 1.10-3.03] and 2.54 [95% CI, 1.11-5.69], respectively). The association was not significant in TC or CLL. In conclusion, we report the incidence of several malignancies in a nationwide cohort of HCV-infected persons. Although the delayed diagnosis of HCV probably has resulted in an underestimation of the risk, this study showed a significantly increased risk of NHL and MM.