Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of ten indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD4 ⁺ (n=4), CD8 ⁺ (n=4), CD4 ⁺ /CD8 ⁺ (n=1) and CD4 ^- /CD8 ^- (n=1) cases. Genetic alterations, including recurrent mutations and novel rearrangements, were identified in 8/10 (80%) of these lymphoproliferative disorders. The CD4 ⁺ , CD4 ⁺ /CD8 ⁺ , and CD4 ^- /CD8 ^- cases harbored frequent alterations of JAK-STAT pathway genes (5/6, 82%); STAT3 mutations (n=3), SOCS1 deletion (n=1) and STAT3-JAK2 rearrangement (n=1), and 4/6 (67%) had concomitant mutations in epigenetic modifier genes (TET2, DNMT3A, KMT2D). Conversely, 2/4 (50%) of the CD8 ⁺ cases exhibited structural alterations involving the 3' untranslated region of the IL2 gene. Longitudinal genetic analysis revealed stable mutational profiles in 4/5 (80%) cases and acquisition of mutations in one case was a harbinger of disease transformation. The CD4 ⁺ and CD4 ⁺ /CD8 ⁺ lymphoproliferative disorders displayed heterogeneous Th1 (T-bet ⁺ ), Th2 (GATA3 ⁺ ) or hybrid Th1/Th2 (T-bet ⁺ /GATA3 ⁺ ) profiles, while the majority of CD8 ⁺ disorders and the CD4 ^- /CD8 ^- disease showed a type-2 polarized (GATA3 ⁺ ) effector T-cell (Tc2) phenotype. Additionally, CD103 expression was noted in 2/4 CD8 ⁺ cases. Our findings provide insights into the pathogenetic bases of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and confirm the heterogeneous nature of these diseases. Detection of shared and distinct genetic alterations of the JAK-STAT pathway in certain immunophenotypic subsets warrants further mechanistic studies to determine whether therapeutic targeting of this signaling cascade is efficacious for a proportion of patients with these recalcitrant diseases.