Previous results about the clinical and prognostic significance concerning CD56 expression status in extranodal NK/T cell lymphoma (ENKTL) are controversial due to a small sample size and the heterogeneity nature of this disease. The complete data of 288 patients with early-stage upper aerodigestive tract ENKTL were retrospectively reviewed. One hundred eighty-three patients (63.5 %) had stage I disease, and the primary tumor site of 204 patients (70.8 %) was in the nasal cavity. Sixty patients (20.8 %) were categorized to CD56-negative ENKTL group. The complete remission rate in CD56-positive ENKTL group was 80.6 %, significantly higher than that in CD56-negative ENKTL group (60.8 %, P = 0.005). At a median follow-up time of 69 months, the 5-year and 10-year progression-free survival (PFS) rate were 52 and 41 %, respectively, and the 5-year and 10-year overall survival (OS) rate were 69 % and 68 %, respectively. Patients with primary tumor site located in the nasal cavity or CD56-positive expression had significantly superior PFS and OS (P < 0.05). In multivariate Cox regression model that included age, Ann Arbor stage, lactate dehydrogenase (LDH) level, primary tumor site, chemotherapy regimens, and CD56 expression status, all these six factors remained to be independent prognostic factors for PFS, and the first five factors were independent prognostic factors for OS, while CD56 expression status had a trend to be independently correlated with OS (P = 0.084). In a subgroup analysis according to primary tumor site location, CD56 expression status significantly correlated with survival outcomes in patients with primary nasal cavity involvement (P < 0.05). In conclusion, in this large cohort of patients with early-stage ENKTL, we found that CD56-negative ENKTL had significantly inferior survival outcomes, indicating CD56-negative ENKTL should be regarded as a distinct phenotype, and optimal treatment strategies need to be evaluated further for this entity.