-Inflammatory breast cancer (IBC) is a rare and aggressive subtype with poor prognosis. This retrospective study compares IBC and non-inflammatory breast cancer (NIBC). A total of 67 women with invasive breast cancer who underwent radical mastectomy were included; 19 were diagnosed with IBC and 48 with NIBC. PI3KCA protein expression was evaluated by immunohistochemistry, and tumor infiltrating lymphocytes (TILs) were assessed using histopathological techniques in all cases. Results were correlated with clinicopathological features and molecular subtypes. In IBC, PI3KCA overexpression was mainly observed in triple-negative (31.58%) and luminal (10.53%) subtypes, as well as in grade III tumors (31.58%) (p = 0.498). It was associated with a high Ki67 index (52.63%) (p = 0.381), though not statistically significant. In NIBC, PI3KCA expression was highest in triple-negative tumors (29.16%) (p = 0.162) and absent in luminal subtypes. Expression was present in both high and low Ki67 levels (22.92% each) (p = 0.281). TILs ≥ 50% were found in 15.78% of IBC and 20.83% of NIBC cases. IBC was predominantly associated with grade III and triple-negative subtypes. These findings suggest PI3KCA as a promising prognostic marker of tumor aggressiveness, especially in IBC. Furthermore, TILs may serve as valuable prognostic indicators, warranting further investigation.