Carcinoma in situ (CIS) is part of the histopathologic spectrum of laryngeal disorders where invasive squamous cell carcinoma is the endpoint of cellular disarray. Few reports consider prognostic indicators that predict which lesions become invasive. Forty-one patients with CIS of the glottic larynx were analyzed for risk factors that would predict invasive cancer. Anterior commissure involvement by CIS resulted in 92% conversion to invasive squamous cell cancer compared to 17% of lesions limited to the mobile fold. Epidermal growth factor receptors were also analyzed and were found not to be helpful in predicting invasion. Lesions of the mobile fold should be removed endoscopically and the patient should be observed closely for recurrence. Anterior commissure involvement that is inaccessible to complete laser ablation should be radiated, and the patient should be observed carefully.