ARLTS1--a member of ADP-ribosylation factor family, is a newly described candidate tumour suppressor gene. Recent studies show that a nonsense polymorphism, G446A (Trp149Stop), in ARLTS1 gene is significantly more frequent in familial cancer cases than in sporadic cancer cases. This study presents analysis of the germ-line G446A polymorphism in the ARLTS1 gene among 1686 consecutively collected patients with breast cancer, prostate cancer, malignant melanoma, thyroid papillary cancer or laryngeal cancer in Poland. The G446A allele was present in 1.81% (9/497) breast cancer patients, 1.46% (5/343) prostate cancer patients, 1.76% (7/397) melanoma patients, 1.65% (3/182) thyroid papillary carcinoma patients and 2.68% (8/299) of laryngeal cancer patients. The frequency of this polymorphism in the control group was 1.45% (8/552). Differences in the frequency of the G446A polymorphism between case and control groups were not statistically significant. In addition, there was no significant difference in the number of Cancer Familial Aggregations (CFA) among breast, prostate, thyroid or laryngeal cancer cases harbouring the G446A polymorphism, when compared to the G446A negative cases. Interestingly out of the CFA melanoma cases, 4/6 (66.6%) were found to harbour the change compared to only 20.2% (69/341) sporadic melanoma cases. This difference was statistically significant (p = 0.02, OR = 7.8). The results of this study suggest that the G446A in ARLTS1 gene is probably not associated with an increased risk of sporadic breast cancer, prostate cancer, melanoma, thyroid papillary cancer or laryngeal cancer. Moreover, the G446A polymorphism is not significantly more frequent in CFA cases except for families in which the proband had melanoma. To confirm this result more cases of melanoma should be analysed.