We performed an immunohistochemical analysis of CXCR4/CD184 expression in frozen and paraffin-embedded sections of human peripheral T-cell lymphomas that exhibit a composite Th1 T-cell–like or Th2 T-cell–like immunophenotype, based on expression of Th1-associated markers (CXCR3, CD134/OX40, and CD69) and Th2-associated markers (CD30 and CCR4). In 66 cases examined, CXCR4/CD184 expression correlated significantly with immunoreactivity for other markers of Th2 differentiation (P < .0001). Anaplastic large cell lymphoma, which typically expresses markers of Th2 differentiation, was immunoreactive for CXCR4/CD184 in 22 (88%) of 25 cases. Tumors previously identified as exhibiting a composite Th1-like immunophenotype, which include angioimmunoblastic lymphoma, lymphoepithelioid lymphoma, and other peripheral T-cell lymphomas now termed unspecified, were positive for CXCR4/CD184 in 7 (17%) of 41 cases. These results are consistent with previous findings that a subset of peripheral T-cell lymphomas can be divided into Th1-like and Th2-like categories based on immunoreactivity with a limited set of markers. Our findings also suggest that CXCR4/CD184, which is expressed by a number of malignant neoplasms and may have a role in tumor metastasis, may have a similar function in CXCR4+ T-cell non-Hodgkin lymphomas.