When she took police to the apartment where she said the babysitter, Zenaida Fernandez-Gonzalez, lived, they found that no one had lived in the apartment for five months.
At that time, lead investigator Yuri Mellich said, "I am not disregarding that this person may or may not exist, but Casey Anthony's friends and family have never met this person."
After an extensive search for Gonzalez, a woman with the same name came forward in September to tell authorities she had never met Casey or Caylee. Police cleared her of any involvement.
Casey also claimed to have worked for Universal Studios, but admitted later that that was not true.
Scientists found evidence of body decomposition and traces of chloroform in Casey Anthony's car trunk, according to forensics reports released in October.
Lab reports from the FBI found that a hair strand in the trunk showed "characteristics of apparent decomposition." The hair is "microscopically similar" to hair strands found on Caylee's brush, but the report said it could not conclusively say the hair in the trunk came from the missing girl.
Casey had been considered a "person of interest" in her daughter's disappearance since mid-July after police reported in a bond hearing that they believed they found that evidence of decomposition in the car.
But what unsettled investigator Padilla more than Anthony's imprecise information is her overall attitude.
"She has shown no emotion," Padilla told ABCNews in July. "That's unusual. At the time of the interviews ... she didn't seem concerned and that made this case much stranger."
"She spoke to deputies like she was talking about baseball. How do you get through to someone like that?" he added.
But Anthony revealed the entire range of emotion in videos of jailhouse conversations between her and her parents, which were released Dec. 5.
In the more than 300 minutes of video released by the Orange County Sheriff's Department, Casey Anthony is shown laughing, crying and growing frustrated with the investigation and her family's questions.
When her mother, Cindy Anthony, confronted her with lead Detective Yuri Mellich's suspicions that she had had something to do with Caylee's disappearance, her daughter dodged the issue.
"Yuri [Mellich] has it set in his mind. He thinks you've done something to Caylee," Cindy Anthony told her. At that point, her daughter got up and, when she returned, steered the conversation in a different direction.
Casey Anthony also said that she knows the conversations are being recorded and said,"there are things [she] directly needs to say" to each of her parents.
And to her missing daughter, Caylee, Anthony asked her mother to pass along a message that "Mommy loves her very much, and that she's the most important thing in this entire world to me. And to be brave."
Padilla said last week that the discovery of the skull may provide some certainty in such an uncertain case.
"Time is on the investigation's side now," he told ABC News. "The Anthonys have tried to throw smoke bombs. Now we have the luxury of taking our time. We're going to be methodical."