INTRODUCTION: Comorbidities affect diagnosis and treatments in cancer patients. This study explores the prevalence and patterns of comorbidities in non-small cell lung cancer (NSCLC) patients and their association with survival. MATERIALS AND METHODS: This retrospective population-based cohort study included 1674 incident NSCLC patients. Comorbidities were classified based on the ICD-9-CM system, with 13 disease categories analyzed. Patients with more than two comorbidities were classified into three mutually exclusive and exhaustive latent classes (Latent Class Analysis [LCA]). The optimal number of latent classes was determined by applying the Akaike Information Criterion. Cox regression models were run to assess overall and cancer-specific mortality, adjusting for the comorbidity groups, sex, age, and stage at diagnosis. RESULTS: In 1674 NSCLC patients, the most prevalent medical conditions were respiratory (35.8%) and cardiovascular (33.5%). The Cox regression showed that even one comorbidity is associated with an increased hazard of overall mortality (HR = 1.33, 95%CI: 1.11-1.59, = 0.002). LCA-derived Class-1 (cardiovascular-respiratory and endocrine) reported HR = 1.74 (95%CI: 1.39-2.17, < 0.001), Class-2 (multi-organ) HR = 1.44 (95%CI: 1.18-1.77, < 0.001), and Class-3 (socio-multifactorial-neuro) HR = 1.62 (95%CI: 1.36-1.93, < 0.001). Instead, in patients with one comorbidity, NSCLC-specific mortality showed no significant trend towards increased risk (HR = 1.17, 95%CI: 1.00-1.43, = 0.114). Significant associations emerged between NSCLC-specific mortality and LCA-classes: Class-1: HR = 1.49 (95%CI: 1.20-1.91, = 0.001); Class-2 HR = 1.25 (95%CI: 1.0-1.57 = 0.048); and Class-3: HR = 1.23 (95%CI: 1.00-1.48, = 0.035). CONCLUSIONS: The adverse impact of comorbidities on NSCLC-specific mortality requires their inclusion as risk factors in cancer treatment and prognosis.