Because Juan Diego did not speak Spanish, it has been proposed by multiple authors and analysts that the name Guadalupe, referring to the Virgin of Guadalupe, was likely derived from a word in the Nahuatl language.
 Coatlaxopeuh is a word proposed by Father Mariano Jacobo Rojas of Tepoztlán as a possible Nahuatl origin of the word Guadalupe, the appellation of the Virgin of Guadalupe. The suggestion of a Nahuatl etymology for the Virgin's name was part of the Mexican indigenista debates of the mid 20th century, in which prominent intellectuals reinterpreted Mexican history with a renewed emphasis on the nation's indigenous heritage. In addition to coatlaxopeuh many other proposed Nahuatl etymologies of Guadalupe have been suggested, but in the devotional literature coatlaxopeuh remains the most accepted.
 The earliest suggestion that the word "Guadalupe" was a corruption of an original Nahuatl word was by the priest Luis Becerra y Tanco in 1666. He proposed that since Juan Diego did not speak Spanish, and since the Nahuatl language did not have the voiced consonants "g" or "d", it was likely that the name had originally been a Nahuatl word which was later misheard by Spaniards as “Guadalupe”. He proposed that the original name could have been "tequantlanopeuh" which he translated as "She who originated from the summit of the rocks".
 Father Mario Rojas Sánchez who translated the Nicān Mopōhua suggested the Nahuatl name "Tlecuauhtlapeupeuh," which he translates as "She who emerges from the region of light like the Eagle from fire".
 Scholar Jeanette Rodríguez, citing Xavier Escalada, notes "the Nahuatl language does not contain the letters d and g; therefore Our Lady's name could not have been "Guadalupe". She also presents the theory that Juan Diego and his uncle called the Virgin "Tlecuauhtlacupeuh", saying "The Nahuatl understanding of 'Tlecuauhtlacupeuh' is La que viene volando de la luz como el águila de fuego (she who comes flying from the region of light like an eagle of fire). The region of light was the dwelling place of the Aztec gods, and the eagle was a sign from the gods. To the Spaniards, it sounded like 'Guadalupe' and reminded them of their Virgin at home."
 Rodríguez holds that the Spanish thought of "Guadalupe of Estremadura, Spain. [As] A large number of conquistadors were from the province of Estremadura and quite naturally were devoted to the local patroness. ...the devotion to Our Lady of Guadalupe in Estremadura was reaching its peak at the time of the first contacts between Spain and the New World".
 Rodríguez adds that the name "To the Spaniards...reminded them of their Virgin at home. To the natives, it...referred to a sign that had come from their gods." This allowed each side to see in the story something it "understood and valued, which would inevitably bring them together as a unifying force."
 Gloria Anzaldúa, in her book Borderlands / La Frontera, proposes the indigenous origin of Guadalupe as Coatlalopeuh, which she translates as "She Who Has Dominion over Serpents." She argues that because Coatlalopeuh sounds like Guadalupe, the Spanish saw Coatlalopeuh as parallel or identical to "the dark Virgin, Guadalupe, patroness of West Central Spain" (Page 27). Anzaldúa gives Coatlaxopeuh as a variant name. She sees both versions as being linked historically to Cōātlīcue, whose name means "Serpent Skirt."