Background: Squamous cell carcinoma of the skin (SCC) is the second most common neoplasm in humans and the most frequent in Brazil (80% in the head and neck region, 20% mortality). Brazil is a world leader in organ transplants (more than 30,000 transplants in 2019). The risk of transplant patients (Tx) developing SCC is 65-250 times higher, with deeper infiltration, advanced stage, higher local recurrence, occult metastases and worse survival. Objective: To investigate the prognostic factors of locally advanced cutaneous squamous cell carcinoma (LASCC) of the head and neck region in transplant patients. Methods:16-year retrospective, single-center series of patients with LASCC in the head and neck region who underwent surgical treatment. Were analyzed: clinical and Tx data, clinical/pathological stage, surgical treatment, parotid/regional and distant metastases, recurrence and survival. Results: 156 patients were included: 69.2% women, 65.3 years; mean primary size: 4.24 cm, 66% T3/T4 tumors, 71% grade 2/3 differentiation, 20.5% transplant recipients, follow-up: 33.6 months. Most affected regions: malar/nasal (28.8%), auricular (19.2%). Surgeries: wide resection with reconstruction (58.9%), exenteration (14.1%), temporalectomy (11.5%). Univariate analysis: Recurrence: immunosuppressor drugs (p=0.009), transplanted (p=0.006), compromised margin (p=0.049), Mortality: immunosuppression (p=0.028), Total Resection and reconstruction (p=0.013), Stage(8ed) III-IV (p<0.001), compromised margin (p<0.001), neck metastasis with extranodal extension (p=0.018). Multivariate analysis: Recurrence: Transplanted HR:3.69 (p<0.001), Neck metastasis extranodal extension HR:5.41 (p<0.001), Evolution to Distant metastasis HR:5.27 (p<0.001); Mortality: Neck metastasis extranodal extension HR:1.94, (p=0.032), Compromised Margins HR:1.87 (p=0.001), Main Surgical Procedures: Temporalectomy HR:2.83 (p=0.007); Major Rhinectomy HR:2.47 (p=0.005); Worst Overall Survival: Tx compared to NonTx (p=0.069), Worst Survival with Recurrence: Tx compared to NonTx (p=0.005). Conclusions: The LASCC and Transplanted (immunosuppressed) group present low survival, worse prognosis, high risk of recurrence and mortality outcome, formulation of specific guidelines to standardize treatment and predict outcomes in this population are strictly necessary.