The present study aimed to identify (1) differentially expressed genes (DEGs) in primary ameloblastoma tissues compared to the corresponding normal gingiva samples, (2) hub genes and clusters in the PPI network associated with the primary ameloblastoma, (3) TFs and protein kinases regulating hub genes and TFs, respectively, (4) the most important signaling pathways and BPs enriched in primary ameloblastoma, and (5) approved drugs for possible inhibition or activating the upregulated and downregulated hub genes, respectively. This evidence concerns the gene WEE1 and ameloblastoma.