Cases of CD45-negative acute lymphoblastic lymphoma/leukemia (ALL) immunoreactive for CD99 and Friend Leukemia Integration-1 (FLI-1) can occur and may lead to a misdiagnosis of Ewing sarcoma/peripheral neuroectodermal tumor with critical clinical treatment management implications. The objective of this study was to evaluate a panel of antibodies that would allow greater diagnostic accuracy of ALL and evaluate the frequency of FLI-1 immunoreactivity in a series of ALL cases and an expanded series of T-cell lymphoma subtypes. Immunoreactivity for CD3 was seen in 12/20 (60%), CD20 in 5/20 (25%), CD43 in 19/20(95%), CD45 in 15/20(75%), CD99 in 15/20 (75%), FLI-1, and terminal deoxynucleotidyl transferase (TdT) in 17/20 (85%) cases. Two cases negative for leukocyte common antigen (LCA), CD20, and CD3 were positive for FLI-1, CD99, TdT, and CD43. Two other LCA-negative cases were positive for CD99 but negative for FLI-1. The majority of cases showed immunoreactivity for CD43 and/or TdT. Therefore, CD43 and/or TdT should be included in the immunohistochemical evaluation of small round blue cell tumors. Absence of immunoreactivity for LCA does not exclude ALL and immunoreactivity of FLI-1 is not restricted to Ewing sarcoma/peripheral neuroectodermal tumor. We also report FLI-1 expression in an expanded series of 75 cases of T-cell lymphoma and found high expression in anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma.