Deregulated CMYC gene causes cell transformation and is often correlated with tumor progression and a worse clinical outcome of cancer patients. The transcription factor Myc functions by heterodimerizing with its partner, Max. As a strategy to inhibit Myc activity, we have synthesized three small peptides corresponding to segments of the leucine zipper (LZ) region of Max. The purpose of these peptides is to occupy the site of recognition between Myc and Max located in the LZ and inhibit-specific heterodimerization between these proteins. We have used the synthesized oligopeptides in two lung cancer cell lines with different levels of Myc expression. Results demonstrate that: (i) the three peptides resulted equally effective in competing the interaction between Myc and Max in vitro; (ii) they were efficiently internalized into the cells and significantly inhibited cell growth in the cells showing the highest Myc expression; (iii) one specific peptide, only nine aminoacids long, efficiently impaired the transcriptional activity of Myc in vivo, showing a more stable interaction with this protein. Our results are relevant to the development of novel anti-tumoral therapeutic strategies, directed to Myc-overexpressing tumors.