Over 90% of puppies sold in pet stores are from puppy mills. If you want a purebred dog, find a breed specific rescue. NEVER but from a retail pet store. 

Good breeders don't want amateurs messing with the bloodlines. A good breeder will insist that you spay/neuter the dog (and have you sign an agreement). If you don't comply, the offspring will not be eligible "for papers."

Dogs in these facilities are considered livestock. As such, they are not protected under the same animal cruelty laws that apply to dogs in homes.

Do not let your desire for a puppy or a specific breed override your judgement. If you encounter any of these red flags, don't fall for excuses. And don't ignore that little voice in your head (the one that just asked, "What little voice in my head?) if it's telling you something is not right. Notice if you're overlooking red flags just because you want the puppy. It's better to work with a reputable rescue, breeder, or wait for the breed to show up in an animal shelter.

Have patience.

While not all puppy mills are located in the Midwest, the vast majority of them are.

If they insist on meeting you off site, on a highway, and/or will not let you meet the parent dogs, that's sketchy. Steer clear if they offer shipping. No reputable breeder would ship puppies off. There should be no reason that you cannot visit the breeder's operations. 

Reputable breeders typically stick to one breed and possess a deep understanding of that breed's health and concerns, genetic background, temperament, and official breed standard. If they always have puppies available, it should make you ask how many breeding dogs they have and/or are they forcing females to have back-to-back litters.

Good breeders want to make sure their dogs are going to good homes. If you weren't screened, it's not a good sign. By screening, we mean the breeder will be asking you questions. 

Working with a reputable breeders feels like an adoption. You were screened, they checked references, they asked questions of you to make sure you're prepared to undertake adopting the particular breed you're adopting. If obtaining the puppy was as simple as forking over the money, that's not a reputable breeder.

A reputable breeder will provide paperwork of everything that the puppy has received (vaccines, etc.) and will make sure you understand what is still needed in the way of vaccines and other care. If this is not provided - don't walk, RUN.