To look for subtle evidence of marrow involvement in nasal NK cell lymphoma at diagnosis, we retrospectively studied trephine biopsy specimens from 25 consecutive patients by 2 sensitive techniques: CD56 immunohistochemistry and Epstein-Barr virus-encoded RNA in situ hybridization (EBER ISH). Only 2 patients had marrow involvement by NK cell lymphoma at diagnosis. In 3 additional patients, marrow involvement developed during or after systemic recurrence. All 5 positive cases were revealed by EBER ISH, but only 3 cases showed CD56 immunoreactivity. Among the 5 cases, only 2 were recognized by morphologic assessment. All 5 patients died, often within a short period, compared with a mortality of 50% for patients without demonstrable marrow involvement. Marrow involvement is distinctly uncommon in nasal NK cell lymphoma at diagnosis, and EBER ISH is the most sensitive technique for the demonstration of occult NK cell lymphoma. Despite the low frequency of marrow involvement in nasal NK cell lymphoma, EBER ISH is worthwhile to identify the minor subgroup of patients with a high likelihood of early death due to disease and when autologous bone marrow or peripheral blood stem cell transplantation is contemplated.