Fibroblast growth factor 2 (FGF-2) is a multifunctional cytokine expressed in several tissues and involved in a wide variety of biologic activities, with one low molecular weight (LMW) protein present in the cytosol, which is secreted, acting via its receptors (FGFRs), and four high molecular weight (HMW) proteins located in the nucleus. Fibroblast growth factor receptor (FGFR) family has four (FGFR1-4) transmembrane tyrosine kinase receptors expressed on several cell types, and FGFR-1 has been indicated as a potential molecular target in several types of cancer, including oral squamous cell carcinoma (OSCC). The FGF-2/FGFR-1 expression has been studied in the oral cavity, and it was associated with the wound repair process, the development of benign and malignant salivary gland tumors, besides being related to oral potentially malignant disorders (OPMDs) and OSCC. Hence, we critically review the currently available data on FGF-2/FGFR-1 expression in the normal mucosa and lesions of the oral cavity.