The present study highlighted substantial radiological and prognostic differences between IBCs and SDBCs. From a radiological perspective, patients with IBCs were more likely to show a high breast density compared to SDBCs. This finding is in line with current literature [5-7]. First, it has long been known that higher mammographic density (MD) is a strong independent predictor of BC. On one hand, higher prevalence of high breast density among IBCs than SDBCs observed in our study may explain the “masking effect”. Some studies have shown that increased MD may obscure/hide signs of small tumors on screening mammograms, which grow to become clinically detectable in the interval before the next screen [8]. To overcome the “masking effect” of breast density, Olinder et al. showed that screening digital breast tomosynthesis in women with higher dense breasts have resulted in a significant increase in sensitivity compared to screening digital mammography [9]. Moreover, the ongoing RIBBS study (NCT05675085) will help in defining the optimal screening strategy for young women by stratifying the population based on breast density and BC lifetime risk using specific screening protocols that include digital breast tomosynthesis, ultrasound and magnetic resonance imaging [10]; this is in accordance with the literature [11]. Patients with IBCs were more likely to show, on mammograms opacities/asymmetries and architectural distortions compared to SDBCs, features more common among FN and MS subtypes. First, it should be pointed out that the aim of this study was not to evaluate the ability of radiologists to detect a suspicious mammographic lesion, but rather to evaluate/look for whether IBCs, re-evaluated according to an informed review, have specific radiological/biological features. Patients with IBCs presented a higher burden of high-risk features such as high histological grading, multifocality/multicentricity, lymph node metastases, and a larger tumor size as compared to patients with SDBCs. We found significant percentage of high grade among IBCs (in particular in TIBCs and FN) than SDBCs [12–18]. The paper by Bellio et. all showed a higher prevalence of G3 cancers among IBCs than SDBCs [9]. The majority of cancers (IBCs and SDBCs) included in our study were invasive cancers, as well known in literature and the remaining cases were DCIS: the latter presented a lower prevalence in IBCs than in SDBCs [12,13, 15, 17]. Multifocality was more prevalent in IBCs (including TIBCs and FN) than in SDBCs. Metastases to regional lymph nodes were more prevalent among IBCs (in particular in FN) than SDBCs, as noted by other researchers [13–17]. Our study reported a significant difference in histological distribution: invasive lobular cancer rates were higher in IBCs than SDBCs, particularly among TIBCs. Several studies have compared biomarkers expression between IBCs and SDBCs. All of these studies have reported lower expression of ER and PR in IBCs (in particular in TIBCs) [19-22]. Regarding HER-2 overexpression, data were more controversial. In our study, we observed a higher proportion of ki67 overexpression in IBCs, especially in TIBCs and FN. This result is in agreement with previous studies [13, 17, 22]. We documented a higher prevalence of triple-negative phenotype in IBCs compared to SDBCs, particularly in TIBCs; these findings are consistent with those reported by several studies [12, 13, 15, 16, 22]. In conclusion, the present study revealed that IBCs, especially TIBCs, represent a particular group of cancers with specific characteristics that make them more aggressive, compared to SDBCs, in relation to invasiveness, advanced stage, histopathological features, and molecular phenotype (with the highest rates of high histological grading, triple negative phenotype, invasive lobular cancer)[12,14–17].