Background and Objective: The clinical characteristics and prognosis of primary systemic anaplastic large cell lymphoma (ALCL) are various according to different reports. Anaplastic lymphoma kinase (ALK), a specific marker of primary systemic ALCL, is related with its clinical characteristics and prognosis. This study was to investigate the clinical characteristics and prognosis of primary systemic ALCL, and to explore the expression and clinical significance of ALK. Methods: Clinical data of 57 primary systemic ALCL patients, treated in Cancer Center of Sun Yat-sen University from January 1997 to January 2006, were reviewed. The expression of ALK in 46 tumor specimens was detected by SP immunohistochemistry. Results: The median age of the 57 patients was 30. The male/female ratio was 1.9:1. Of the 57 patients, 33 (57.9%) had B symptoms, 23 (40.4%) had Ann Arbor stage III-IV tumors, and 23 (40.4%) had extranodal disease at diagnosis. All patients received chemotherapy. Of the 56 evaluable patients, 40 (71.4%) achieved complete remission. The overall response rate was 96.4%. With a median follow-up of 49.1 months, the median time to progression was 35.2 months and the expected 5-year survival rate was 65.2%. The expected 5-year survival rate was significantly higher in low/ low-intermediate International Prognostic Index (IPI) risk group than in high-intermediate/high IPI risk group (68.9% vs. 33.3%, p = 0.010). The positive rate of ALK was 63.0% in the 46 cases detected. Compared with ALK-negative patients, ALK-positive patients were younger (p = 0.001) and had higher expected 5-year survival rate (p < 0.01). Multivariate analysis confirmed the independent prognostic values of ALK expression, primary disease site and lactate dehydrogenase (LDH) level. Conclusions: Primary systemic ALCL usually occurs in young patients, with good response to chemotherapy and good prognosis. No ALK expression, high-intermediate/high IPI, extranodal disease and elevated LDH level are correlated to unfavorable prognosis. © 2009 Sun Yat-Sen University Cancer Center.