STRUCTURED AbstractOBJECTIVEPhoton absorption remote sensing (PARS) is a new laser-based microscope technique that permits cellular level resolution of unstained fresh, frozen, and fixed tissues. Our objective was to determine whether PARS could provide image quality sufficient for diagnostic assessment of breast cancer needle core biopsies (NCB).DESIGNWe PARS imaged and virtually H&E stained seven independent unstained formalin fixed paraffin-embedded breast NCB sections. These identical tissue sections were then subsequently stained with standard H&E and digitally scanned. Both the 40x PARS and H&E whole slide images were assessed by seven breast cancer pathologists, masked to the origin of the images. A concordance analysis was performed to quantify the diagnostic performances of standard H&E and PARS virtual H&E.RESULTSThe PARS images were deemed of diagnostic quality and pathologists were unable to distinguish the origin of the images above that expected by chance. The diagnostic concordance on cancer vs. benign was high between PARS and conventional H&E (98% agreement) and there was complete agreement for within PARS images. Similarly, agreement was substantial (kappa > 0.6) for diagnosis of specific cancer subtypes. PARS virtual H&E inter-rater reliability was broadly consistent with the published literature on diagnostic performance of conventional histology NCBs across all tested histologic features.CONCLUSIONS AND RELEVANCEPARS was able to provide images on unstained tissues slides that were diagnostically equivalent to conventional H&E. Due to its ability to non-destructively image fixed and fresh tissues, and the suitability of the PARS output for artificial intelligence assistance in diagnosis, this technology has the potential to improve both the speed and accuracy of breast cancer diagnosis.