Changes in the serum level of the soluble form of CD30 (sCD30) in a patient with adult T-cell leukemia/lymphoma were monitored throughout the indolent phase, acute crisis, and relapse. The level of sCD30 was elevated prior to the development of laboratory data abnormalities. In addition, the elevated sCD30 level was associated with clinical manifestations in the lung, including malignant pleural effusion, which is a diagnostic criterion of acute crisis. The sCD30 level correlated with clinical aggressiveness, and the lung lesion reoccurred on the same side as the original lesion. These data suggest that microenvironment or minimal residual disease formed in the right lung. Pathological examination of lung biopsy at the indolent phase revealed accumulated CD30+ cells among CD3+CD45RO+ T cells. The serum level of sCD30 correlated with clinical aggressiveness, indicating that the small population of CD30+ cells plays an important role in the progression of adult T-cell leukemia/lymphoma.