Carcinoma in benign-mixed tumor (CBMT) is common in the female canine mammary gland and comprises malignant epithelial between benign mesenchymal elements. This study investigated the morphological aspects of 29 CBMT and their immunophenotypical profiles, by using an immunohistochemistry panel based on five molecular markers—estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), and human epidermal growth factor receptor 1 (EGFR). From these, CBMT was classified into four subtypes: luminal A, luminal B, HER2-like, basal-like, and normal. “In situ” and invasive carcinomatous components were analyzed and compared. Histological grade I carcinoma was observed in 16 cases (55.2%) of the tumors analyzed, grade II in 10 cases (34.5%), and grade III in three cases (10.3%). The invasive carcinomatous component has shown, more frequently, luminal A (12/29 cases, 41.4%), followed by basal-like phenotype (8/29 cases, 27.6%). There was high concordance between immunophenotypical profiles of the in situ and invasive carcinomatous components (kappa coefficient = 0.816, ?? < 0 . 0 0 1 ). We concluded that CBMT predominantly has features of low-grade neoplasms of malignancy. The various immunophenotypic profiles suggest the origin of these lesions in more than one cell type (luminal and myoepithelial). 1. Introduction Mammary glands are the most frequent site of neoplasias in female dogs, and mammary cancer is one of the leading causes of death in these animals [1, 2]. These tumors have similarities to human breast neoplasms, and therefore, their etiopathogeny and biological features are of great interest [3, 4]. Mixed tumors (MTs) are histologically characterized by a mixture of epithelial components (ductal and/or acinous cells and myoepithelial cells) within an apparent mesenchymal stroma capable of producing various amounts of myxoid, chondroid, and bone tissues. These neoplasias can be benign-mixed tumors or can undergo malignant transformation, giving rise to carcinomas in benign-mixed tumors (CBMTs) [5, 6]. Several studies have investigatedthe relationship betweenprognostic factors and breast carcinomasin female dogs,but little is knownabout the biological behaviorand prognosisof these neoplasms [7, 8]. The molecular-based classification system adopted for breast cancer is a valuable tool for assessing prognosis and investigating similarities between the canine and human tumor types. According to thisdata,at least five different molecular subtypes ofhuman breast carcinomas were identified, based
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