The cell nucleus is a structurally complex and dynamic organelle ensuring key biological functions. Complex relationships between nuclear structure and functions require a better understanding of the three-dimensional organization of the genome and of the subnuclear compartments. Quantitative image analysis coupled with spatial statistics and modeling is a relevant approach to address these questions. In this chapter, we describe a step-by-step procedure to process images and to test a spatial random model for the distribution of nuclear objects using chromocenters as an example. More elaborate models can be designed on the basis of the random model by introducing additional and more complex constraints to better fit observations and to question determinants of these spatial organizations.