AbstractBackgroundThe floor of mouth (FOM) is a common site of oral squamous cell carcinoma (SCC). The purpose of this study was to investigate pathological predictors of survival in FOM SCC.MethodsWe conducted a retrospective study of 54 consecutive patients undergoing surgery for FOM SCC. Pathological parameters were extracted from histological reports with original pathology slides re‐reviewed by 2 pathologists for missing data.ResultsOn univariate analysis, depth of invasion >10 mm (p = .009), lymphovascular invasion (LVI; p < .001), noncohesive invasive front (p = .006), perineural invasion (PNI; p = .003), and nodal metastases (p = .02) were significant predictors of overall survival. On multivariate analysis, LVI (p = .009) and invasive front (p < .001) remained significant. Postoperative radiotherapy improved survival in patients with LVI, PNI, and nodal metastases, and was just outside significance for noncohesive invasive front (p = .06).ConclusionLVI is an adverse prognosticator in FOM SCC and indicates postoperative radiotherapy. Further study is required to investigate the importance of invasive front. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1528–E1534, 2016