Elevated levels of soluble CD30 (sCD30) are linked with various T-cell neoplasms. However, the relationship between sCD30 levels and the development of adult T-cell leukemia (ATL) in human T-cell leukemia virus type 1 (HTLV-1) carriers remains to be clarified. We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers. We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sCD30 concentration at baseline was significantly higher in cases than in controls (median 65.8, range 27.2-134.5 U/mL vs. median 22.2, range 8.4-63.1 U/mL, P=0.001). In the univariate logistic regression analysis, a higher sCD30 (≥30.2 U/mL) was significantly associated with ATL development (odds ratio 7.88 and the 95% confidence intervals 1.35–45.8, P = 0.02). Among cases, sCD30 concentration tended to increase at the time of diagnosis of aggressive-type ATL, but the concentration was stable in those developing the smoldering-type. This suggests that sCD30 may serve as a predictive marker for the onset of aggressive-type ATL in HTLV-1 carriers.