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To distinguish the similarities or differences between T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), we retrospectively analyzed the clinical, immunophenotypic, cytogenetic, and molecular characteristics in 37 children diagnosed between December 1990 and December 2003. Comparative Expressed Sequence Hybridisation (CESH) was used to determine gene expressing profile in both diseases. Twenty two patients suffered from T-ALL and 15 patients were diagnosed as T-LBL. Immunophenotyping demonstrated a more immature phenotype in T-ALL and a more mature phenotype in T-LBL. Cytogenetic and molecular genetic aberrations were found in 82% of T-ALL compared with 73% of T-LBL. By CESH gene expression profiling, the investigated cases were segregated into two groups that largely corresponded with T-ALL and T-LBL. The clinical presentation and cytogenetic characteristics are largely similar for T-ALL and T-LBL supporting the concept that both represent a spectrum of one single disease. The differences that were found between both neoplasms, in particular in their phenotype and in their expression profile may suggest that most T-ALL derive from a T-cell progenitor of the bone marrow, while thymocytes represent the normal counterpart of T-LBL.