CD44 is a broadly distributed family of cell surface glycoproteins. The expression of CD44H has been documented in both Hodgkin lymphoma and non-Hodgkin lymphoma. CD44V6 has been associated with more aggressive behavior in non-Hodgkin lymphoma, but such a correlation has not been established in Hodgkin lymphoma. In addition, the utility of CD44 and CD44V6 in the subclassification of Hodgkin lymphoma in paraffin-embedded tissues has not previously been evaluated. The current study included formalin- or methacarn-fixed, paraffin-embedded tissue specimens from 42 patients with Hodgkin lymphoma (25 nodular sclerosis, three interfollicular, four lymphocyte-rich classic Hodgkin, six lymphocyte predominant, and four mixed cellularity). The clinical stage of the study population at initial presentation ranged from stage IA to IVB. Evaluation of CD44H and CD44V6 (Novocastra) was performed by ABC immunoperoxidase technique after heat-induced epitope retrieval. In the six cases of lymphocyte predominant Hodgkin, the neoplastic cells lacked reactivity with CD44H reminiscent of their normal germinal center counterparts. On the other hand, classic Hodgkin lymphoma showed variable membranous and Golgi reactivity in the neoplastic cells in all cases irrespective of disease stage at presentation. In all cases, the neoplastic cells lacked reactivity with CD44V6 except for three one lymphocyte-predominant, one interfollicular, and one nodular sclerosis), all of which represented recurrent cases. In conclusion, CD44 evaluation is useful in the distinction between lymphocyte predominant and classic Hodgkin lymphoma. The presence of CD44H expression has no relation to the clinical stage of the disease at presentation or recurrence. CD44V6 is detected in a minority of cases irrespective of the histologic subtype and its presence may be associated with recurrence. There was no correlation between disease stage at presentation and the expression of CD44V6.