Background and Aims Lymphovascular invasion (LVI) is an indicator of lymph node metastasis and poor prognosis in various cancers including squamous cell carcinoma (SCC). Despite being easily resectable and having little potential for LVI; SCC displays aggressive behavior and often results in the death of the patient. With this in mind, it may be useful to investigate the clinical, pathological, and microRNA expression profile associated with LVI in SCC. Methods We evaluated the histological hallmarks associated with LVI from 16 formalin fixed paraffin embedded (FFPE) tissue samples (10 LVI−, 6 LVI+). We also quantified the expression of 10 microRNAs (hsa‐miR‐21‐5p, hsa‐miR‐21‐3p, hsa‐miR‐155‐5p, hsa‐miR‐196a‐5p, hsa‐miR‐375, hsa‐let‐7d‐5p, hsa‐miR‐146b‐3p, hsa‐miR‐221‐5p, hsa‐miR‐205‐5p, hsa‐miR‐491‐5p), which have been previously identified to play a role in SCC development, using real time‐PCR with the Qiagen miRCURY LNA SYBR Green PCR Kit. Results We observed a significant upregulation of microRNA‐155, microRNA‐196a, microRNA‐375, and microRNA‐221 in cases with lymphovascular invasion. Morphologically, we identified poor differentiation, dysplasia, loss of membrane polarity, high nuclear to cytoplasmic ratio, and the presence of squamous nests as defining features of LVI. Additionally, we found a gender bias and observed a tendency toward lymphatic invasion in lesions presenting around the perineal and abdominal regions. Conclusion We speculate that this profile may have prognostic significance and could guide the clinician in their treatment protocols for patients matching our genetic, demographic, and morphologic profile.