Diffuse-type tenosynovial giant cell tumor (D-TGCT) and localized-type tenosynovial giant cell tumor (L-TGCT) share common genomic aberrations and histopathological features, but the former has a more aggressive nature and a higher recurrence rate, leading to worse prognoses for patients. In this study, single-cell RNA sequencing (scRNA-seq) on human D-TGCT and L-TGCT lesions is conducted to discover transcriptional differences. A unique cluster of tumor cells in D-TGCT is identified that regulated differentiation of CD34(+) fibroblasts into MMP3(+) fibroblasts or APOE(+) fibroblasts via COL6A3 - (ITGAV + ITGB8) interaction. The APOE(+) fibroblasts further activated IL-1B(+)CCL20(+) macrophages through the CXCL12/CXCR4 axis. IL-1B(+)CCL20(+) macrophages and MMP3(+) fibroblasts participated in local aggression of D-TGCT. Two effective biomarkers, ROR1 and PRKD1 are also identified and validated, to predict disease recurrence. This study not only clarified the underlying mechanisms of aggressive behavior in D-TGCT but also provided a theoretical basis and potential targets for intervention into and treatment of this disease.