Abstract: Provided herein are methods of detecting or inhibiting melanoma growth based on Gab2 protein expression. Gab2 protein was found to be either amplified and/or overexpressed in melanoma. Gab2 protein expression correlated with clinical melanoma progression and higher levels of expression were seen in metastatic melanomas compared to primary melanoma and melanocytic nevi. Over-expression of Gab2 potentiates, whereas silencing of Gab2 reduces, migration and invasion of melanoma cells. Gab2 mediated hyperactivation of Akt signaling in the absence of growth factors and inhibition of the PI3K-Akt pathway decreased Gab2-mediated tumor cell migration and invasive potential. Gab2 over-expression resulted in enhanced tumor growth and metastatic potential in vivo. These results demonstrate a previously undefined role for Gab2 in melanoma tumor progression and metastasis.