BACKGROUND: Small bowel adenocarcinoma (SBA) is a malignant tumor with a relatively low prevalence. Metastasis, especially liver metastasis (LM), is an important prognostic indicator of poor prognosis in patients with SBA. Due to the rarity of SBA, there is currently a lack of research on the characteristics of liver metastases in small intestine cancer. The aim of this study is to investigate the molecular characteristics associated with metastasis in SBA and to explore the specific molecular combinations related to LM. METHODS: A retrospective study was performed on patients with SBA who were admitted to Zhejiang Hospital and Affiliated Hangzhou First People's Hospital from July 2013 to July 2022. Sequencing with tissue was performed using a 1,021-gene panel. The least absolute shrinkage and selection operator (LASSO) algorithm was used to identify the genes for predicting LM from SBA. RESULTS: A total of 97 patients with SBA, including 48 patients without metastasis, 29 with LM, and 20 with extrahepatic metastasis (EHM), were enrolled in this cohort. The five genes with the highest mutation frequency in the overall samples were CONCLUSIONS: This study elucidated the molecular characteristics of metastatic SBA and found that