Pleomorphic　invasive　lobular　carcinoma　(pILC)　is　a　distinct　morphological　variant　of　invasive　lobular　carcinoma　(ILC),　which　is　more　aggressive　than　classic　invasive　lobular　carcinoma　(cILC)　with　worse　overall　prognosis.　It　is　critical　to　distinguish　between　pILC　and　cILC　for　management　and　treatment　of　patients.　Multiphoton　microscopy　(MPM),based　on　two-photon　excited　fluorescence　(TPEF)　and　second　harmonic　generation　(SHG),　produces　subcellular　resolution　images　to　show　detailed　information　on　structure　and　cell　morphology　of　tissue　sections　without　staining.　In　this　work,　MPM　was　introduced　for　label-free　identification　of　normal　breast　lobules,　pILC　and　cILC,　which　is　consistent　with　haematoxylin　and　eosin　(H&E)　staining.　Furthermore,　analysis　of　nuclear　area　is　used　to　quantitatively　reflect　their　cytological　characteristic.　These　results　demonstrate　that,　MPM　has　the　ability　to　distinguish　between　normal　breast　lobules,　cILC,　and　pILC　by　histopathological　features,　which　can　provide　additional　indicators　to　determine　adequate　treatment　strategies　of　patients　with　pILC　for　pathologists　and　surgeons.　In　the　future,　MPM　may　be　used　as　a　diagnostic　tool　of　lobular　cancer　into　routine　clinical　use.　©　2019　SPIE.