This study aimed to explore the feasibility of amide proton transfer weighted (APTw) imaging in discriminating fat-poor angiomyolipoma (AML) from clear cell renal cell carcinoma (ccRCC). 19 ccRCC patients and 9 fat-poor AML patients were recruited for APTw imaging. ccRCC group showed significantly higher MTRasym compared to fat-poor AML group (P < 0.05). High AUC of 0.827 in ROC analysis validated the efficacy of APTw imaging in differentiating fat-poor AML from ccRCC. With these findings, APTw imaging may be considered an effective method providing added clinical value in differentiating fat-poor AML from ccRCC.