Background: Perineural invasion (PNI) is an important histologic factor that plays a significant role in cutaneous tumors' aggressiveness. Objectives: We sought to evaluate the incidence, features, and outcomes of cutaneous squamous cell carcinoma with PNI in patients treated with Mohs micrographic surgery (MMS). Method: This prospective, multicenter, case series included all patients in Australia treated with MMS for squamous cell carcinoma with PNI who were monitored by the Skin and Cancer Foundation Australia between 1993 and 2002. The parameters recorded were patient demographics, duration of tumor, site, preoperative tumor size, recurrence before MMS, histologic subtypes, postoperative defect size, and recurrence at 5 years after MMS. Results: Seventy patients were given a diagnosis of PNI. PNI was more common in men (77.1%) and in previously recurrent tumors (P = .04). The moderately and poorly differentiated histologic subtypes were more likely to be associated with PNI (P < .0001). Tumor sizes before excision, postoperative defect sizes, subclinical extension, and mean number of MMS levels were significantly larger in cases with PNI compared with cases without PNI (P < .0001, P < .0001, P = .002, and P < .0001, respectively). Most patients with PNI (52.9%) were treated with adjunctive radiotherapy. In all, 25 patients completed a 5-year follow-up post-MMS, and two of them (8.0%) were given a diagnosis of recurrence. Conclusion: Although PNI is an uncommon feature of cutaneous squamous cell carcinoma, when present, it is associated with larger, more aggressive tumors, and the risk of recurrence is higher. This emphasizes the importance of tumor excision with margin control and long-term patient monitoring.