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Simple Summary: The expression of the mechanosensory Piezo2 channel has already been described in different malignant tumors. There is discordance in the literature regarding breast carcinoma, with its expression described either as decreased or increased in neoplasms with respect to benign tissue. A retrospective cohort of 125 patients whose breasts were resected for carcinoma was chosen to determine the relationship between Piezo2 and different clinical and histological variables. A significant association was found with the Ki67 proliferation index, with a tendency for most proliferative tumors to be positive for Piezo2. In the last decade, a group of Ca2+ channels called Piezo were discovered, demonstrating a decisive role in the cellular response to mechanical stimuli and being essential in the biological behavior of cells regarding the extracellular compartment. Several investigations have suggested a potential role in carcinogenesis, with a tumor suppressor role in some cases but increased expression in several high-grade neoplasms. Regarding Piezo2 expression in mammary gland neoplasms, a protective role for Piezo2 was initially suggested, but a subsequent study demonstrated a relationship between Piezo2 expression and the highly aggressive triple-negative phenotype of breast carcinoma. A cohort of 125 patients with clinical follow-up was chosen to study Piezo2 expression and clarify its clinical implications using the same immunohistochemical evaluation performed for other breast carcinoma parameters. Fisher's exact test was chosen to identify potential relationships between the different variables. A significant association was found with the Ki67 proliferation index, but not with mitoses. The tendency of most proliferative tumors was to have an increased score for Piezo2. A similar association was found between Piezo2 expression and perineural invasion. [ABSTRACT FROM AUTHOR]