The aim of this study was to determine the translocation and copy number change of the C‐MYC gene in patients with laryngeal dysplasia and laryngeal squamous cell carcinoma (LSCC), and to evaluate the prevalence of such expression in relation to the normal‐dysplasia‐carcinoma sequence. Fluorescent in situ hybridization (FISH) was applied on formalin‐fixed paraffin‐embedded blocks of 93 laryngeal lesion specimens (14 normal epithelium, 15 mild dysplasia, 18 moderate dysplasia, 16 severe dysplasia, 9 carcinoma in situ, and 21 invasive carcinoma). C‐MYC translocation was not observed in all laryngeal tissue. The high frequency for C‐MYC copy‐number increased (100%) in invasive carcinoma: 57.14% amplifications and 42.86% gains, and the positive rate of C‐MYC amplification and copy‐number change increased with the increasing severity of laryngeal lesions (P < 0.0001). The results suggest that C‐MYC may be activated by gain/amplification in LSCC and precancerous lesions. Thus, C‐MYC may play an important role in promoting LSCC progression, and early FISH detection of C‐MYC may be exploited to set a screening test for laryngeal dysplasia. Diagn.Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.