The aim of the present study was to establish the frequency of separate and combinatorial copy number changes of EGFR, C-MYC, ZNF217 and CCND1 in larynx cancer. The impact of these aberrations on tumor stage, metastatic potential and tumor grade was considered. A total of 240 larynx tumor samples, included in a preexisting tissue microarray were successfully hybridized by fluorescent in situ hybridization for all 4 loci. Normal gene copy numbers of all loci were established in 71 tumors (29.58%). In 169 tumors (70.42%) at least one aberration was observed. The frequency of aberrations was significantly associated with a higher risk for the development of metastasis (p< 0.0002). In addition, higher frequency of aberrations was detected in stage IV tumors (71.43%) in comparison with stage I-III tumors (59.32%, p= 0.13). Single abnormalities were detected in 90 tumors (53.25%), while double or higher changes were found in 79 tumors (46.75%). The single abnormalities neither the combinatorial ones when analyzed separately showed an association with tumor stage, metastatic potential or tumor grade. We conclude that EGFR, C-MYC, ZNF217 and CCND1 aberrations play an important role in larynx tumorigenesis related to invasive tumor potential.