Background Great advances have been made in the diagnosis, molecular pathogenesis and treatment of acute lymphoblastic leukemia (ALL) in the past decade. Due to the lack of large population-based studies, the recent trends in the incidence and geographic variations of ALL in Shanghai, China have not been well documented. To better understand the incidence and epidemiological features of ALL in Shanghai, we conducted a retrospective survey based on the database from the Shanghai Center for Disease Control and Prevention (CDC) and the medical records in all large-scale hospitals in Shanghai, especially those 30 major hospitals with hematology department.Methods According to the data from Shanghai CDC, 544 patients, with a median age of 32 years (ranging 1.2-89years), were diagnosed as de novo ALL from January 1, 2002 to December 31, 2006, and they were followed up until December 31,2007.Results The average annual incidence of ALL in Shanghai was 0.81/100000. The incidence in men (0.86/100 000)was slightly higher than that in women (0.75/100 000). The age-stratified incidence showed that the incidence was 2.31/100 000 in patients ≤17 years old, 0.54/100 000 in those 18-34 years old, 0.46/100 000 in those 35-59 years old,and 0.94/100 000 in those ≥60 years old. Moreover, there were substantial geographic variations in the incidence of ALL,with the incidence in Chongming county, an island in the east of Shanghai city being 0.60/100 000, much lower than those of other districts. Both French-American-British (FAB) and World Health Organization (WHO) classification systems were applied in the present study. Eighty-eight patients were diagnosed as L1 (26.2%), 193 L2 (57.4%), and 55 L3 (16.4%). For 302 patients with immunophenotypic results, 242 were identified as B cell origin (80.1%), 59 as T cell origin (19.5%), and 1 as biphenotype (0.4%). The leukemia cells in 61 patients co-expressed one or two myeloid antigen (20.2%). For 269 patients with cytogenetic results, the incidences of t(9;22) in patients aged ＜10, 11-17, 18-44, 45-59and ≥60 years old were 4.2%, 11.4%, 19.2%, 23.1% and 5.3%, respectively.Conclusion Compared with the previous data, the incidence of ALL is increased in Shanghai, and has a geographic distribution characteristic.