Malignant Eyelid Tumors in Italy (2020–2024): Toward Personalized Epidemiologic Insights from Two Referral Centers

<b>Background/Objectives:</b> Eyelid malignancies represent a clinically relevant subset of cutaneous tumors of the head and neck, with significant functional and cosmetic implications. While basal cell carcinoma (BCC) is the predominant subtype, geographic differences in the relative frequency of squamous cell carcinoma (SCC) and rarer histotypes have been reported. This study aimed at comparing the distribution of malignant eyelid tumors diagnosed in two Italian referral centers, namely Cagliari (Sardinia) and Milan (Lombardy) between 2020 and 2024, and to explore demographic and epidemiologic correlates. <b>Methods</b>: A total of 250 malignant eyelid tumors were analyzed: 130 from Cagliari and 120 from Milan. BCC was the most common histological subtype overall (83.2%), followed by SCC (12.4%) and other malignancies (4.4%). The proportion of SCC was significantly higher in Milan (18.3%) compared to Cagliari (6.9%, <i>p</i> = 0.04). Logistic regression confirmed Milan as an independent risk factor for SCC (OR 3.79; 95% CI 1.57-9.18; <i>p</i> = 0.003). Male gender also emerged as a predictor of SCC (OR 2.50; 95% CI 1.10-5.67; <i>p</i> = 0.029). Most cases occurred in patients ≥70 years; cases under 50 years were rare (≈3%). <b>Conclusions</b>: BCC remains the predominant malignant eyelid tumor in Italy; significant inter-regional variability exists, with a higher proportion of SCC in northern Italy. These findings highlight the role of environmental, demographic, and organizational factors, and emphasize the need for multicenter registries. Region-specific insights may inform personalized prevention and surveillance strategies for eyelid malignancies. These findings may support the development of region-tailored prevention models and contribute to the growing field of personalized oncology within ophthalmology.