Somatic mutations affecting genes in the cAMP/PKA (protein kinase A) signaling pathway have been described as causative for the pathogenesis of benign unilateral adrenocortical adenomas associated with cortisol over secretion. These include predominantly somatic mutations in the PRKACA gene which encodes the catalytic subunit α of PKA. In addition, mutations in the GNAS gene, coding for the stimulatory G protein α, have been observed in approximately 10% of cortisol producing adenomas (CPA). The mutations render PKA signaling constitutively active and are therefore involved in cortisol over secretion of these tumors. Despite the prominent role of the cAMP/PKA pathway in the pathogenesis of unilateral CPA, also mutations in the CTNNB1 gene, encoding β-catenin, were identified in CPA. However, mutations in β-catenin are not limited to CPA and are not associated with cortisol secretion since they were predominantly found in endocrine-inactive adenomas (EIA) and might hence contribute to tumorigenesis in adrenocortical tissues. In this review, recent findings in the pathogenesis of benign adrenocortical tumors with a particular focus on the cAMP/PKA signaling pathway are summarized.