Papillary Thyroid Carcinoma (PTC) is the most common subtype of thyroid cancer that is the most prevalent in the endocrine system. According to worldwide reports, its prevalence rate has been increasing in recent decades. The Discovery of DNA sequencing methods and molecular diagnostic techniques provides an insight into the understanding of PTC molecular biology and as well as in thyroidology, which opens a new perspective in finding molecular markers. Aligning cytological diagnostic methods with molecular behavior studies creates promising tools for better decision-making strategies for preoperative conditions to distinguish between benign from malignant thyroid nodules in challenging cases and limit unnecessary surgeries. Extensive studies have been performed on identifying the genes involved in PTC development and their prognosis. Currently, clinical and pathological features of the tumour (such as size, extrathyroid and lymph node invasion, and capsular invasion) are used to predict the prognosis of papillary thyroid cancer. In this review, we tried to summarize fundamental signaling pathways affecting PTC and the most important genetic alterations, including point mutations in proto-oncogenes and chromosomal rearrangements, as well as up/down-regulation of certain micro RNAs (miRNA) as an epigenetic change. Briefly, some of the most commonly altered genes in PTC are BRAF, RAS, RET, PAX8, PPARγ, and miRNAs like mir-146b, mir-221, mir-222, and mir-181b.