Twenty alleles for the locus human leukocyte antigen (HLA-A) and 46 for the HLA-B locus were detected in Jordanians. This indicates the existence of high polymorphism in this area. The most frequent HLA class I alleles found were A*0201 (0.1344), B*0713 (0.1724), and C*0502 (0.1793). Twenty-six different alleles in the Jordanian population were identified for the DRB1 locus being the DRB1*0704 (0.2552), DRB1*0401 (0.1965), and DRB1*1501 (0.0896) the most frequent. Common DQA1 alleles were DQA1*0201 (0.2690), DQA1*0301 (0.2414), and DQA1*0501 (0.1724). Three-loci haplotype heterogeneity was common: 38 HLA class II haplotypes were identified, of which the most frequently observed was DRB1*0401-DQA1*0301-DQB1*0302 (0.1793). In addition, as expected, 220 different five-loci haplotypes with several unusual allelic combinations were observed, although many of them are pan-European haplotypes. The most frequent five-loci haplotype was the A30-B7-DRB1*03-DQA1*0501-DQB1*0201 (0.0138). It seems that the specific Jordanian haplotypes are the following: the A31-B7-DRB1*04/07-DQA1*0301/0201-DQB1*0302/0202 haplotypes (0.0103) and the A1-B7-DRB1*07-DQA1*0201-DQB1*0202, A2-B7-DRB1*04-DQA1*0301-DQB1*0302, A11-B7-DRB1*07-DQA1*0201-DQB1*0201 haplotypes but at lower frequencies (0.007). A tree analysis of HLA class I and class II alleles were made for several Caucasian populations and individual genetic distances calculated. The haplotype frequencies, genetic distances, and dendrograms do not reveal great differences as compared with those in other Mediterranean countries and Western Europeans populations. Our results suggest that both HLA class I and class II polymorphism (but especially the former) of the Jordanian population demonstrates considerable heterogeneity, which reflects ancient and recent admixture with neighboring populations, and important human migratory trends throughout the history.