Age is a major risk factor for solid tumors, including breast cancer. The majority of elderly breast cancer patients have oestrogen-dependent tumors, thus, tamoxifen is widely administered. However, it has been noted that tamoxifen-related thrombotic events are not exceptional. Due to the increasing prevalence of comorbidity, including vascular diseases, with age, such events are more frequently observed in the aged patients. Formestane, a selective steroidal aromatase inhibitor, may represent a therapeutic option after failure with tamoxifen, or in the presence of vascular diseases contraindicating its administration. The present report provides a new clinical experience on a consecutive series of 45 elderly breast cancer women affected by moderate to severe degree of comorbidity and disability measured by a Comprehensive Geriatric Assessment (CGA) scale validated on oncological patients. Formestane was given intramuscularly at the dose of 250 mg every 2 weeks. The study included 31 patients who had metastatic disease, and 14 who received formestane as an adjuvant treatment. Median age was 74 years (range 65-93), with nine patients > 80 years. Median ECOG Performance Status (PS) was one. The more frequent comorbidities observed in our series were arthrosis-arthritis (64.4% of patients), hypertension (44.4%), vascular diseases (35.5%), CNS diseases (28.8%). Twenty percent of patients presented at least one dependency in Activities of Daily Living (ADL) and 51.2% in Instrumental Activities of Daily Living (IADL). The treatment was well tolerated - only two patients interrupted formestane because of minor adverse reaction at the injection site and generalised itching. In particular Formestane was not responsible for any worsening of pre-treatment comorbidities, especially hypertension and vascular diseases. Objective responses (OR) were observed in 11.1% of advanced patients, while the disease was stabilised in 51.8% subjects. Median duration of OR was 12 months; median overall survival was 11 months. Among patients receiving formestane as adjuvant treatment, three relapsed, with a time to failure (TTF) of 12 months. Formestane is effective and minimally toxic in an elderly breast cancer population with comorbidities and disabilities measured by CGA.