In microscopy imaging, colocalization between two biological entities (e.g., protein-protein or protein-cell) refers to the (stochastic) dependencies between the spatial locations of the two entities in the biological specimen. Measuring colocalization between two entities relies on fluorescence imaging of the specimen using two fluorescent chemicals, each of which indicates the presence/absence of one of the entities at any pixel location. State-of-the-art methods for estimating colocalization rely on post-processing image data using an adhoc sequence of algorithms with many free parameters that are tuned visually. This leads to loss of reproducibility of the results. This paper proposes a brand-new framework for estimating the nature and strength of colocalization directly from corrupted image data by solving a single unified optimization problem that automatically deals with noise, object labeling, and parameter tuning. The proposed framework relies on probabilistic graphical image modeling and a novel inference scheme using variational Bayesian expectation maximization for estimating all model parameters, including colocalization, from data. Results on simulated and real-world data demonstrate improved performance over the state of the art.