The MAPK/ERK (mitogen - activated protein kinase/extracellular signal-regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems (ligands, transmembrane receptors and cytoplasmic secondary messengers) to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. The genes, coding the signaling cascade proteins (e.g., RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. This review is focused mainly on genetic alterations in genes, coding signaling pathway proteins. Moreover, it is additionally pointed out that genetic, as well as epigenetic DNA changing via aberrant methylation of several tumour suppressor and thyroid-specific genes are associated with tumour aggressiveness, being a jointly responsible mechanism for thyroid tumorigenesis. The understanding of this molecular mechanism provides access to novel molecular therapeutic strategies for inhibiting oncogenic activity of signaling pathways.