T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder and can cooccur in the context of pure red cell aplasia (PRCA). The aim of the current study was to analyze the signal transducer and activator of transcription 3 (STAT3) mutation status and its clinical significance in T-LGLL. We found STAT3 mutations in 21.4% of patients with T-LGLL. High ß2-MG (ß2-microglobulin) levels (P = 0.005), neutropenia (P = 0.018) and PRCA (P = 0.001) all displayed a significant association with STAT3 mutations. In univariate analysis, treatment-free survival (TFS) was affected by STAT3 mutation status (P=0.008) and ß2-MG (P = 0.006). Our results demonstrate the remarkable correlation of STAT3 mutation with PRCA, neutropenia and ß2-MG.