INTRODUCTION: Mature plasmacytoid dendritic cell proliferation (MPDCP) is generally considered to be associated with myeloid neoplasms. To date, case reports of MPDCP associated with lymphoid malignancies are exceedingly rare. CASE REPORT: Herein, we report the case of a 69-year-old male who presented with multiple enlarged preauricular, cervical, inguinal, and axillary lymph nodes. A comprehensive analysis, including morphology, immunophenotyping, and histopathology, confirmed a diagnosis of early T-cell precursor acute lymphoblastic leukemia with MPDCP. Single-cell RNA sequencing identified a transcriptional continuum between T-ALL blasts and pDCs, indicating a potential developmental relationship between these cell types. During the 9-month follow-up period, the patient survived and achieved complete remission. CONCLUSION: This case highlights the presence of MPDCP in lymphoid malignancies and utilizes single-cell RNA sequencing technology to provide insights into the potential link between pDC and lymphocyte differentiation and development. However, further studies are needed to confirm these findings and explore their clinical implications.