Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma in which T-cell subsets have not been studied specifically. We reviewed 24 cases of NLPHL and compared flow cytometric results with those of 13 progressively transformed germinal centers (PTGC) cases, 78 nonspecific reactive hyperplasia (RH) cases, and 31 classical Hodgkin lymphoma (CHL) cases. A double-positive (CD4+CD8+) T-cell population was present in 58% of NLPHL cases, constituting 10% to 38% of T cells. The cells were CD3+, CD5+, CD2+, CD7+, CD1a- and terminal deoxynucleotidyl transferase-. Similar CD4+CD8+ T cells were identified in 38% of PTGC cases (P = .31), 4% of RH specimens (P < .00001), and 6% of CHL specimens (P < .0001). The presence of a CD4+CD8+ T-cell population in NLPHL may reflect an activated or reactive T-cell subset and should not lead to a misdiagnosis of T-cell lymphoma. This population may be a clue to the diagnosis of NLPHL, particularly in cases with limited tissue.