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We reexamine the problems of computer-aided classification and pairing of human chromosomes, and propose to jointly optimize the solutions of these two related problems. The combined problem is formulated into one of optimal three-dimensional assignment with an objective function of maximum likelihood. This formulation poses two technical challenges: 1) estimation of the posterior probability that two chromosomes form a pair and the pair belongs to a class and 2) good heuristic algorithms to solve the three-dimensional assignment problem which is NP-hard. We present various techniques to solve these problems. We also generalize our algorithms to cases where the cell data are incomplete as often encountered in practice.