Inframe insertion and deletion/insertion (delins) mutations of the IL7R gene in exon 6 have recently been reported in childhood T-cell acute lymphoblastic leukemia (T-ALL). The recurrent nature of the IL7R mutations in the same region strongly suggests that the IL7R mutations may play an important role in the pathogenesis of childhood T-ALL. The aim of this study was to address whether IL7R exon 6 mutation occurs in other human tumors besides childhood T-ALL. For this, we analyzed 1792 tumor tissues from various origins, including 432 hematologic and 1360 nonhematopoietic tumors by single-strand conformation polymorphism analysis to detect the exon 6 mutations. Overall, we found 10 IL7R exon 6 mutations in seven hematologic malignancies (three childhood T-ALL [12%], one adult T-ALL [7%], two childhood precursor B-cell acute lymphoblastic leukemia (B-ALL) [2%] and one adult acute myelogenous leukemia (AML) [1%]) and three nonhematopoietic malignancies (one lung cancer [0.6%] and two colorectal cancer [0.5%]), but none in other tumors. IL7R mutations detected in hematologic tumors were exclusively inframe insertion and delins mutations, whereas those detected in non-hematologic tumors were missense and frameshift mutations. Our data indicate that IL7R exon 6 inframe mutations occur not only in childhood T-ALL but also other acute leukemias at slightly lower frequencies. Our data suggest that the IL7R mutations may contribute to the development of diverse types of acute leukemias, and that possible therapies targeting the IL7R exon 6 mutation should include not only childhood T-ALL but also T-ALL, childhood precursor B-ALL, and adult AML.