Embodiments associated with classifying a region of tissue using features extracted from nodules and surrounding structures. One example apparatus includes a feature extraction circuit configured to automatically extract a first set of quantitative features from a nodule represented in at least one CT image, and automatically extract a second set of quantitative features from the lung parenchyma region immediately surrounding the nodule represented in the at least one CT image a feature selection circuit configured to select an optimally predictive feature set from the first set of quantitative features and the second set of quantitative features and a training circuit configured to train a classifier using the optimally predictive feature set to assign malignancy risk to a lung nodule represented in a CT image of a region of tissue demonstrating lung nodules. A prognosis or treatment plan may be provided based on the malignancy risk.