Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, poses significant diagnostic challenges due to its overlap with benign inflammatory skin diseases and the absence of specific symptoms. Accurate early diagnosis and stratification of patients by progression risk are essential for effective treatment. This study proposes a proof-of-concept for integrating T-cell receptor (TCR) clonality analysis with somatic mutation profiling to enhance diagnostic confidence and prognostic accuracy in early-stage MF. This study's methodology comprised the analysis of nine patients with early MF (stages IA/IB) using whole-exome sequencing and TCR repertoire profiling. The analysis revealed the presence of clonal TCR rearrangements in seven patients, while somatic mutations were identified in two. A notable finding was a recurrent chromosome 7 trisomy in these two cases. The patients were stratified into three molecular profiles: (1) somatic mutations with clonal TCR rearrangement (n = 2), (2) clonal TCR rearrangement without somatic mutations (n = 4), and (3) neither somatic mutations nor clonal TCR rearrangement (n = 3). These findings emphasise the heterogeneity of MF and underscore the limitations of relying solely on TCR clonality or mutation burden for diagnosis. This study underscores the potential of somatic mutations as diagnostic markers to distinguish MF from benign conditions and as prognostic indicators for disease progression. A combined genetic approach may refine treatment decisions, particularly for patients with higher tumor cell fractions and pronounced genetic alterations. Despite the limited size of the cohort, the results advocate for larger, multi-center studies to validate these findings and integrate genetic analyses into routine MF management.