Nematode infections such as Ascariasis are important health problems in underdeveloped countries, most of them located in the tropics where environmental conditions also promote the perennial co-exposure to high concentrations of domestic mite allergens. Allergic diseases are common, and most of patients with asthma exhibit a predominant and strong IgE sensitization to mites. It is unknown whether co-exposure to Ascaris lumbricoides and the domestic mites Blomia tropicalis and Dermatophagoides pteronyssinus potentiates Th2 responses and IgE sensitization, thereby modifying the natural history of allergy. Recently, we obtained experimental evidence of a high cross-reactivity between the allergenic extracts of these invertebrates, involving well-known allergens such as tropomyosin and glutathione transferases. There is indirect evidence suggesting that the clinical impact of these findings may be important. In this review, we discuss the potential role of this cross-reactivity on several aspects of allergy in the tropics that have been a focus of a number of investigations, some of them with controversial results.