Axillary lymph node metastases of occult breast cancer (CUPAx) is an unusual condition that represents both a diagnostic and therapeutic challenge. The first steps in the diagnostic work-up of patients with CUPAx are the histological analysis of the lymph node metastasis and the execution of basic breast diagnostic imaging (mammography and ultrasound). In the case of occult breast cancer, breast Magnetic Resonance (MR) must be performed. Breast MR identifies a suspicious lesion in many patients and second-look ultrasound detects a corresponding ultrasound alteration in about half of cases, allowing the performance of a US-guided biopsy. In the case of an MR-only lesion, MR-guided biopsy is mandatory. We present a case of CUPAx in which contrast-enhanced spectral mammography (CESM) is used to help the detection of occult breast cancer and to guide stereotactic vacuum breast biopsy (VABB). CESM is a new breast imaging technique that is proving to have good performance in breast cancer detection and that is showing potential in the identification of occult breast cancer in a CUPAx setting. The use of an innovative and personalized breast imaging approach in breast cancer patients improves diagnostic possibilities and promises to become the focus in decision strategies.