Envision this immense region as four clusters. Panajachel and Lake Atitlán lie at the southeastern corner of the region, and are most visitors' first encounter with the highlands. Chichicastenango and the El Quiché heartland are to the north, although most visitors don't make it past Chichi to Santa Cruz del Quiché and Nebaj farther north. Quetzaltenango, the country's second largest city, and its orbit of mountain-market towns form a third bunch of places to visit. Off toward the Mexican border, Huehuetenango and Todos Santos Cuchumatán are the final, less-visited cluster and the heart of the country's Mam culture.
Lago Atitlán. A ring of indigenous communities around an easily accessible, gleaming lake watched over by three volcanoes has drawn visitors for more than four decades. One visit and you'll understand why.
Chichicastenango. The center of Mayan Quiché culture reveres the rituals of the past, but manages to worship commerce too with its world-famous, twice-weekly, you-gotta-see-it market. Less-visited towns to the north of Chichi let you delve further into Quiché tradition.
Quetzaltenango. Hip, educated Quetzaltenango might be Guatemala's second-largest city, but its proud residents concede second place to no one. The real attraction of "Xela," to use the city's beloved original name, is its orbit of communities where indigenous tradition rules.
Huehuetanango. The less-visited region just east of the Mexican border is anchored by the easy-to-reach, medium-size city that everyone calls "Huehue." Todos Santos Cuchumatán, one of the country's most fascinating indigenous communities, is worth the time if you're up to a rugged trip.