A retrospective single-center cohort study was conducted among women aged 45–74 years who participated to a BC regional mammographic screening program at the Breast Unit (BU) of Rimini Hospital (Italy) with EUSOMA accreditation between January 2018 and July 2023: in this period, 169.024 screening mammograms were performed. The program was based on the European Guidelines for Quality Assurance in Mammographic Screening [1]. Women aged 45–49 and those aged 50–74 were followed up through digital mammography every 1 year and every 2 years, respectively. Mammograms were interpreted by two radiologists and, in case of discrepancies, a third radiologist acted as an arbitrator. Between January 2018 and July 2023, a total of 233 IBCs were identified through active case searches which involved consulting BU database; 18 of these were excluded due to missing data (women who contacted our BU for symptoms receiving a first evaluation but did not complete the whole diagnostic–therapeutic process at our BU). Among 215, a group of 115 women who had received histological diagnosis of BC, evaluated and treated at our BU, randomized by age and year of cancer diagnosis, was selected and included in this study (15 women aged 45–49 and 100 women aged 50–74). In addition, 832 SDBCs were reported during the same period. A control group matched for age and year of cancer diagnosis was randomly selected among the screen-detected cancers (n = 229, matched 1:2¸ 44 women aged 45–49 and 185 aged 50–74). Clinical and therapeutic information routinely gathered through questionnaires administered during each screening round were extracted from the BU database. Breast composition on mammography was assessed using the visual method based on the classification of ACR BI-RADS Atlas 5th edition and were collapsed into two groups: “low breast density” (categories A and B) and “high breast density” (categories C and D) [2]. Some tumor characteristics and prognostic features were also obtained from the BU database. Information regarding tumor biomarkers were detected from the Department of Pathology databases. Following standard guidelines, positivity for ER, PR, and ki-67 was determined based on the presence of more than 20% positively stained cells [3]. According to gene expression profiles, BCs were classified into four major molecular phenotypes: Luminal A and Luminal B, HER-2 phenotype, triple-negative phenotype [3, 4]. For the classification of IBCs and for breast composition determination, a retrospective evaluation was conducted by two radiologists, using screening mammograms and diagnostic mammograms (n = 115). It should be pointed out that this paper did not consider performance assessment parameters: an informed evaluation was made and shared by two radiologists who then agreed on final IBCs categorization. Initially, screening mammograms were reviewed by radiologists and classified into three groups: positive (findings suspicious for malignancy), negative (no abnormalities detected), and minimal signs (features difficult to detect or lacking clear malignant features). In agreement with the ACR BI-RADS Atlas (5th edition), suspicious findings were classified as opacities/asymmetries, architectural distortions, and microcalcifications [2]. In a subsequent review, the radiologists examined screening and diagnostic mammograms alongside histological information to determine whether there was a correspondence between mammograms-related abnormalities and the site of the subsequent IBC. IBCs were definitively categorized into five groups according to European Guidelines recommendations: true interval breast cancer (TIBC), false negative (FN), minimal sign (MS), occult cancer (OC) and unclassifiable cases (UC). Statistical analysis was conducted using the IBM SPSS (version 26.0) statistical software. A multivariate analysis was performed to compare differences in proportions among IBCs, IBCs subtypes, and SDBCs using Chi-square tests. All p values ≤ 0.05 were considered statistically significant. Logistic regression analysis was conducted to assess the impact of certain patient-related and tumor-related features on the odds of developing a TIBCs. Results are reported as hazard ratio (HR) [95% confidence interval (C.I.)].