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Simple Summary: The inositol-trisphosphate receptor (IP3R) is a key player in physiological and pathological intracellular calcium signaling. The objective of the present study was to assess the putative value of the three IP3R subtypes as prognostic biomarkers in breast cancer. We found that IP3R3 is the most strongly expressed subtype in breast cancer tissue. Furthermore, IP3R3 and IP3R1 are significantly more expressed in invasive breast cancer tissue than in non-tumor tissue. In contrast to IP3R1 and IP3R2, the expression of IP3R3 was positively correlated with prognostic factors including tumor size, regional node invasion, histologic grade, proliferation index, and hormonal status. By analyzing public databases, we found that the expression of all IP3R subtypes is significantly correlated with the overall survival and disease-free survival of patients with breast cancer. We conclude that relative to the other two IP3R subtypes, IP3R3 expression is upregulated in breast cancer and is correlated with prognostic factors. We strongly believe that our results will open up new perspectives with regard to the link between IP3Rs and breast cancer aggressiveness. Breast cancer is the leading cause of cancer death among women in worldwide and France. The disease prognosis and treatment differ from one breast cancer subtype to another, and the disease outcome depends on many prognostic factors. Deregulation of ion flux (especially Ca2+ flux) is involved in many pathophysiology processes, including carcinogenesis. Inside the cell, the inositol-trisphosphate receptor (IP3R) is a major player in the regulation of the Ca2+ flux from the endoplasmic reticulum to the cytoplasm. The IP3Rs (and particularly the IP3R3 subtype) are known to be involved in proliferation, migration, and invasion processes in breast cancer cell lines. The objective of the present study was to evaluate the potential value of IP3Rs as prognostic biomarkers in breast cancer. We found that expression levels of IP3R3 and IP3R1 (but not IP3R2) were significantly higher in invasive breast cancer of no special type than in non-tumor tissue from the same patient. However, the IP3R3 subtype was expressed more strongly than the IP3R1 and IP3R2 subtypes. Furthermore, the expression of IP3R3 (but not of IP3R1 or IP3R2) was positively correlated with prognostic factors such as tumor size, regional node invasion, histologic grade, proliferation index, and hormone receptor status. In an analysis of public databases, we found that all IP3Rs types are significantly associated with overall survival and progression-free survival in patients with breast cancer. We conclude that relative to the other two IP3R subtypes, IP3R3 expression is upregulated in breast cancer and is correlated with prognostic factors. [ABSTRACT FROM AUTHOR]