AIM: To investigate the clinicopathological features of cranial-nasal-orbital communicating lesions and identify key diagnostic indicators for differentiating benign and malignant neoplasms. METHODS: The retrospective cohort study analyzed 74 histologically confirmed cases stratified by anatomical involvement at the Wuhan Union Hospital between January 2010 and December 2020: Group A (orbital-nasal group, n=29), Group B (orbital-cranial group, n=27), and Group C (cranial-nasal-orbital group, n=18). Clinicopathological profiles including symptom presentation, histopathology, and invasion patterns were systematically evaluated. RESULTS: The cohort comprised 49 (66.2%) benign and 25 (33.8%) malignant lesions. Compared with benign lesions, malignant lesions had a shorter onset time (12mo vs 2.5mo, P=0.004) and resulted in poorer vision (0.6 vs 1.53, P=0.025). Headache was reported in 28.6% of patients with benign lesions, but none in those with malignant lesions (P=0.002). Conjunctival congestion and edema were observed in 32.7% of patients with benign lesions and 60% of patients with malignant lesions (P=0.028). The ethmoid sinus was the most frequently invaded site (35 cases). Malignant lesions showed greater invasion in the nasal cavity (28.0% vs 0, P=0.000) and anterior cranial fossa (40.0% vs 8.2%, P=0.003) than benign lesions. The orbital-cranial group was more likely to invade through osseous foramina compared with the orbital-nasal group (P=0.002). Neurogenic tumors predominated benign cases (34.7%), whereas blood derived (28%) and glandular tumors (28%) were most prevalent in malignant subgroups. The proportion of malignant tumors in multi-disciplinary combined surgery was higher than that of benign lesions (61.5% vs 38.5%). CONCLUSION: Malignant cranial-nasal-orbital communicating lesions exhibit distinct clinicopathological signatures characterized by rapid progression, aggressive anterior fossa and nasal region, and severe visual morbidity.