Background: Stereotactic breast biopsy is a standard intervention for evaluation of "microcalcification-only" lesions. However, an expensive stereotactic device and radiologic expertise are necessary for this procedure. We herein report a non-stereotactic technique involving the combination of wire localization and vacuum-assisted breast biopsy (VABB) under ultrasound (US) guidance. Methods: Twenty-two consecutive patients with category 3 or 4a microcalcification only as shown by mammography underwent the above-mentioned non-stereotactic combination method involving US-guided wire localization and VABB. The location of the microcalcification was measured by manual stereotaxis, and the microcalcification was confirmed by specimen mammography after the procedure. Results: The mean number +/- standard deviation of removed cores and calcified cores was 28.4 +/- 13.4 and 2.2 +/- 0.9, respectively. In one case, the procedure was repeated 3 times. The histologic diagnoses were fibrocystic change (n=14), fibroadenoma (n=4), sclerosing adenosis (n=1), usual ductal hyperplasia (n=2), and atypical ductal hyperplasia (n=1). Conclusions: "Microcalcification-only" breast lesions can be easily evaluated with the combination of non-stereotactic US-guided wire localization and VABB. This would be an effective diagnostic technique for breast lesion which reveals only microcalcification.