The objective of this research was to determine whether biopsy of the breast using a percutaneous intact specimen sampling device influences the underestimation rate of ductal carcinoma in situ (DCIS) compared to a vacuum-assisted core needle biopsy (VACNB) device. This study was a retrospective comparison of two series of 800 consecutive patients that underwent stereotactic biopsy of the breast for mammographic lesions presenting as microcalcifications classified by our institution as Breast Imaging Reporting and Data System (BI-RADS) 4 or 5. In the first series of patients (n = 800), a VACNB device was used; in the second series (n = 800), a vacuum-assisted percutaneous intact specimen biopsy (VAPIB) device was used. Initial diagnoses were made from the histopathologic examination of the tissue retrieved at biopsy. Lesions presenting as DCIS or atypical ductal hyperplasia (ADH) after percutaneous biopsy were then compared to the histopathologic analysis of specimens retrieved at surgical biopsy. DCIS upgrades were defined as cases in which the diagnosis of the stereotactic biopsy was DCIS and the diagnosis of the subsequent surgical excision was infiltrating ductal carcinoma (IDC). ADH upgrades were defined as cases in which the diagnosis of the stereotactic biopsy specimen was ADH and the diagnosis of the surgical excision was DCIS, lobular carcinoma in situ (LCIS), or IDC. The lesions retrieved by both biopsy techniques yielded a similar pathology distribution. Underestimation of DCIS occurred less frequently (p = 0.06) in the biopsy samples taken using the intact biopsy device (1/31, 3.2%) as compared to biopsy samples taken using the core needle biopsy device (7/36, 19.4%). No significant adverse events were reported. Breast biopsy can be performed safely and accurately using a vacuum-assisted percutaneous intact specimen sampling device. In this study, such a device trended toward fewer underestimations of DCIS at biopsy compared to the vacuum-assisted core needle sampling biopsy method.