Leiomyosarcoma of the prostate is an extremely rare neoplasm. It represents less than 0.1% of all prostate malignancies. It is considered to have a poor prognosis, an aggressive nature, and high metastatic potential. Additionally, the relationship between radiation exposure for the treatment of primary prostatic cancer and the occurrence of leiomyosarcoma as second cancer at the irradiated site is rare, with unknown etiology. We reported a 72-year-old male known case of prostate adenocarcinoma with radio-hormonotherapy for six years who presented with acute urinary retention. Magnetic resonance imaging revealed a large malignant obstructive prostate with direct invasion of surrounding organs and multiple metastases. Trans-urethral resection of the prostate was performed, and the histopathology result showed high-grade leiomyosarcoma. The patient passed away after four months due to multiorgan failure. In conclusion, there may be a causal relationship between radiation therapy to the prostate and the development of prostate leiomyosarcoma.