Feline mammary carcinoma (FMC) is a prevalent and aggressive cancer with high metastatic potential. Few tissue biomarkers have been reported to help evaluate disease progression in FMC. This study aimed to analyze the tissue proteomic profiles of metastatic feline mammary carcinoma (mFMC) and non-metastatic FMC (NmFMC) across various histological grades (HGs) and histological types (HTs) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).