Transcription of natural killer (NK) cell antigen receptors (NKRs), such as CD94, NKG2, and killer immunoglobulin-like receptors (KIRs), is developmentally regulated and clonally distributed. We have shown a restricted KIR repertoire (rKIR-R) without monoclonal T-cell receptor rearrangement (mTCR-R) supports a NK lineage in nasal-type extranodal NK/T-cell lymphoma (NTENL) but does not correlate with clinical outcomes. Developing NK cells express first CD94, then NKG2A, NKG2E, and finally NKG2C. This sequence suggests an immature CD94- and a mature CD94+ subtype of NTENL. Using a rKIR-R without a mTCR-R as a criterion in 25 cases of NTENL, we confirmed a true NK lineage in 19 cases, including 10 CD94+ and 9 CD94- patients by reverse transcriptase-polymerase chain reaction (RT-PCR). Eight of the 10 CD94+ patients but only 2 of the 9 CD94- patients survived beyond 1 year (median survival, 60 months versus 10 months by Meier-Kaplan survival analysis, P =.026 by Cox F test). The remaining 6 patients had a rKIR-R plus a mTCR-R, suggesting mixed NK/T differentiation. They were CD94- by RT-PCR, found predominantly in young women, and had a median survival of 35 months. Thus, on the basis of the transcripts of NKRs, a division of NTENLs into CD94+, CD94-, and mixed NK/T types reflects a true biologic divergence with different clinical behaviors.