Acromegaly is caused by excessive GH secretion from pituitary adenomas. Transphenoidal surgery is the first-choice treatment, but new drug therapies (e.g. somatostatin analogues, SSA) offer promising avenues for medical treatment. Complementary diagnostic tools may assist this strategy, helping to refine drug choice. Here, we investigate the associations between radiological features and molecular phenotype of pituitary tumours from acromegalic patients. This observational study included 17 acromegaly patients (38.4±15.6 years; 64.7% women), diagnosed from 2007 to 2012 at the Endocrinology and Nutrition Unit of the Reina Sofia Hospital, in whom surgery, radiology and molecular phenotyping of the adenoma was carried out. Magnetic resonance was performed to localise the tumours, which were all macroadenomas (94.6%) at diagnosis except for one microadenoma. Anteriorposterior mean diameter (APD) was 18.3±6.6 mm, inferiorposterior diameter (IPD) 18.8±6.7, and left-right diameter (LRD) 17.9±6.4 mm. Average volume was 33.36 mm3. Extrasellar growth was observed in 73.3%, suprasellar growth in 60%, right sphenoid sinus invasion in 26.7%, left sinus invasion in 20%, and 20% in both sinus. Compared to isointense adenomas, T2 hyperintense tumours showed greater IPD (23.4±5.3 vs 14.3±5.4 P=0.009), LRD (21.2±4.5 vs 14.6±7.2 P=0.035), total volume (4.5±2.6 vs 2.2±3.1 P=0.025), and Knosp index (2.9±1.2 vs 1.1±1.5 P=0.036). T2 hyperintense adenomas had higher dopamine receptor subtype-5 (DR5) expression (P=0.038)) and Ki67 (P=0.044). Adenoma IPD directly correlated with expression of DR5 (Rho+0.770 (P=0.006)) and somatostatin receptor subtype-3 (sst3) (Rho+0.549 (P=0.034)); and DR5 expression correlated with APD (Rho+0.735 (P=0.010)). Adenoma volume was directly associated with sst3 (Rho+0.535 (P=0.038)) and DR5 (Rho+0.736 (P=0.010)) expression. Knosp index directly correlated with all diameters: APD (P<0.001), IPD (P<0.001), LRD (P=0.002); tumour volume (P<0.001); sst3 (P=0.015); and Ki67 (P=0.044). Our results reveal significant correlations among key pre-surgical radiological parameters and specific molecular phenotypic features of pharmacological relevance in GH-producing adenomas. Future studies should explore the molecular basis of these findings and their potential value in helping to select the appropriate medical therapy for these patients.