This study involved 40 ER-negative female patients with invasive breast cancer, aged between 25 and 88 years, diagnosed at Emergency County Hospital of Craiova, Romania, during a two-year interval (2010-2011). All patients that took part in the study were subjected to a preoperative mammography exam, and later to HP and IHC exams, in order to detect the ER, PR and HER2 status. These exams were followed by CISH in ambiguous HER2 cases. The tumor detection method was palpation in 16 cases, whereas in 24 cases the method used was the screening mammography. Histopathologically, the analyzed tumors were infiltrative ductal carcinoma (35 cases), lobular carcinoma (one case), mucinous (two cases) and metaplastic carcinoma (two cases). Depending on the status of the oncoprotein HER2, the 40 ER-negative female patients included in the study formed two groups: the ER-negative, HER2-positive (11 cases, 27.5%) formed the first group and the ER-negative, HER2-negative (29 cases, 72.5%) formed the second group. Depending on the expression of the receptors for progesterone, 60% of cases were classified as triple negative mammary carcinomas (ER-, PR-, HER2-). The comparative study of the ER-negative, HER2-positive and the ER-negative, HER2-negative mammary carcinomas showed that the tumors of the ER-negative, HER2-positive group were mostly high degree cancers (80% vs. 56%), with negative progesterone receptors (81.81% vs. 48.27%), associated with axillary lymph node metastasis (63.63% vs. 48.27%), and were detected at a higher cancer stage (II/III) (81.81% vs. 62.06%). Regarding the mammographic features, the ER-negative HER2-positive breast cancers are more likely to be irregular masses (62.5% vs. 33.33%), with spiculated margins (45.45% vs. 6.9%), frequently associated with dense or heterogeneously dense breast (82% vs. 69%) and pleomorphic calcifications (62.5% vs. 28.57%) comparative with ER-negative HER2-negative cancers that were more frequently round/oval mass, with indistinct margins and a great variety of morphological types of calcifications. The correlations between imaging and clinical aspects, together with the biomarker expression in breast cancers may sooner suggest the biological characteristics of these tumors, thus hinting at their evolution and helping to identify female patients with invasive breast cancer that will positively respond to an aimed therapy.