In individuals with a history of renal cell carcinoma (RCC), mediastinal lymphadenopathy is frequently attributed to metastatic recurrence. However, secondary malignancies, despite their rarity, should also be considered. During routine follow-up examinations, a 63-year-old male with a history of renal cell carcinoma demonstrated progressive mediastinal lymphadenopathy. This was initially suspected to be a recurrence of renal cell carcinoma (RCC). The diagnosis of metastatic prostate adenocarcinoma was confirmed by prostate biopsy and elevated prostate-specific antigen (PSA) levels, as determined by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Treatment with androgen deprivation therapy (ADT) and chemotherapy was initiated after the patient was diagnosed with metastatic prostate cancer. This case underscores the critical role of EBUS-TBNA in the accurate diagnosis of patients with a history of RCC who demonstrate atypical mediastinal lymphadenopathy. The provision of tissue samples for histopathological analysis by EBUS-TBNA facilitated the differentiation between metastatic recurrence and secondary malignancies. Comprehensive diagnostic methods, including tumor marker analysis, immunohistochemistry, and tissue biopsy, are essential for accurate diagnosis. EBUS-TBNA is indispensable for accurate diagnosis, especially in differentiating metastatic recurrence from secondary malignancies, as it provides a minimally invasive method of tissue access for precise evaluation.