Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, commonly affecting the external genitalia and perianal area of the elderly with unclear pathogenesis. Metabolomics provides a novel perspective for uncovering the metabolic mechanisms of a verity of cancers. Here, we explored the metabolome of EMPD using an untargeted strategy. Results showed that a total of 896 metabolites were identified and 87 metabolites including 37 up-regulated and 50 down-regulated significantly in EMPD were sought out. This study was the first to reveal the metabolome profile of EMPD. Our results demonstrate that IDO1/TDO2-initialized KYN metabolic pathway may play a vital role in the development and progression of EMPD, which may serve as a potential therapeutic target for treating EMPD.