We propose partitioning-based methods to facilitate the classification of 3-D binary image data sets of regions of interest (ROIs) with highly non-uniform distributions. The first method is based on recursive dynamic partitioning of a 3-D volume into a number of 3-D hyper-rectangles. For each hyper-rectangle, we consider, as a potential attribute, the number of voxels (volume elements) that belong to ROIs. A hyper-rectangle is partitioned only if the corresponding attribute does not have high discriminative power, determined by statistical tests, but it is still sufficiently large for further splitting. The final discriminative hyper-rectangles form new attributes that are further employed in neural network classification models. The second method is based on maximum likelihood employing non-spatial (k-means) and spatial DBSCAN clustering algorithms to estimate the parameters of the underlying distributions. The proposed methods were experimentally evaluated on mixtures of Gaussian distributions, on realistic lesion-deficit data generated by a simulator conforming to a clinical study, and on synthetic fractal data. Both proposed methods have provided good classification on Gaussian mixtures and on realistic data. However, the experimental results on fractal data indicated that the clustering-based methods were only slightly better than random guess, while the recursive partitioning provided significantly better classification accuracy.